Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: MYO6 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_004999.3(MYO6):c.475G>A (p.Glu159Lys)

CA135641

45163 (ClinVar)

Gene: MYO6
Condition: nonsyndromic genetic deafness
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 5cc1b9df-7aa4-471a-b98b-ffb43f4fe7c0
Approved on: 2025-01-15
Published on: 2025-03-28

HGVS expressions

NM_004999.3:c.475G>A
NM_004999.3(MYO6):c.475G>A (p.Glu159Lys)
NC_000006.12:g.75832925G>A
CM000668.2:g.75832925G>A
NC_000006.11:g.76542642G>A
CM000668.1:g.76542642G>A
NC_000006.10:g.76599362G>A
NG_009934.1:g.88734G>A
NG_009934.2:g.88733G>A
ENST00000369975.6:c.475G>A
ENST00000369977.8:c.475G>A
ENST00000369985.9:c.475G>A
ENST00000462633.3:c.475G>A
ENST00000627432.3:c.475G>A
ENST00000653423.1:c.475G>A
ENST00000653917.1:c.475G>A
ENST00000660420.1:c.*431G>A
ENST00000662184.1:c.475G>A
ENST00000662603.1:c.475G>A
ENST00000663400.1:c.475G>A
ENST00000664209.1:c.475G>A
ENST00000664640.1:c.475G>A
ENST00000671923.1:c.475G>A
ENST00000672093.1:c.475G>A
ENST00000369975.5:c.475G>A
ENST00000369977.7:c.475G>A
ENST00000369981.7:c.475G>A
ENST00000369985.8:c.475G>A
ENST00000615563.4:c.475G>A
ENST00000627432.2:c.475G>A
NM_001300899.1:c.475G>A
NM_004999.4:c.475G>A
NM_001300899.2:c.475G>A
NM_001368136.1:c.475G>A
NM_001368137.1:c.475G>A
NM_001368138.1:c.475G>A
NM_001368139.1:c.475G>A
NM_001368140.1:c.475G>A
NM_001368865.1:c.475G>A
NM_001368866.1:c.475G>A
NR_160538.1:n.707G>A
NR_160539.1:n.807G>A
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 23
PVS1 PM6 PM2 PM3 PM1 PM4 PM5 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 PS4 PS2 PS3 PS1 PP4 PP1 PP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.475G>A variant in MYO6 is a missense variant predicted to cause substitution of glutamic acid by lysine at amino acid 159 (p.Glu159Lys).​ The filtering allele frequency of this variant is 0.013% for South Asian chromosomes by the Genome Aggregation Database v4 (18/91064 with 95% CI), which meets no population allele frequency criteria (PM2_Supporting, BS1, and BA1 are not met). However, this variant is also present in 0.8% (257/29596) of Ashkenazi Jewish chromosomes, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss variants (BA1). This variant has not been reported in the literature in individuals affected with hearing loss. Therefore, given the lack of contradictory evidence, this variant is classified as benign based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BA1. (ClinGen Hearing Loss VCEP specifications version 2; 01.15.2025).
Met criteria codes
BA1
This variant is present in 0.8% (257/29596) of Ashkenazi Jewish chromosomes, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss variants.
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
http://gnomad.broadinstitute.org/variant/6-76542642-G-A
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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