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: SLC26A4 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_000441.1(SLC26A4):c.2291C>T (p.Thr764Met)

CA132713

43546 (ClinVar)

Gene: SLC26A4
Condition: Pendred syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: edaf7951-7b12-42e2-855d-4a2dc61b69c8
Approved on: 2025-02-19
Published on: 2025-03-18

HGVS expressions

NM_000441.1:c.2291C>T
NM_000441.1(SLC26A4):c.2291C>T (p.Thr764Met)
NC_000007.14:g.107712594C>T
CM000669.2:g.107712594C>T
NC_000007.13:g.107353039C>T
CM000669.1:g.107353039C>T
NC_000007.12:g.107140275C>T
NG_008489.1:g.56960C>T
ENST00000644269.2:c.2291C>T
ENST00000644846.1:c.947C>T
ENST00000265715.7:c.2291C>T
ENST00000492030.2:n.477C>T
NM_000441.2:c.2291C>T
More

Uncertain Significance

Not Met criteria codes 26
PS2 PS4 PS3 PS1 PP4 PP1 PP2 PP3 PM3 PM1 PM4 PM5 PM6 PM2 BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP1 BP4 PVS1

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

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.2291C>T (NM_000441.2(SLC26A4):c.2291C>T (p.Thr764Met)) variant is a missense variant predicted to cause substitution of threonine by methionine at amino acid 764. The highest MAF in gnomAD v4.0.0 is 0.03221 % (2/6022 alleles) in the Middle Eastern population. The next highest MAF in gnomAD is 0.0175 % (13/74302 alleles) in the African/African American population (no population codes met by either frequency). In-silico predictons are conflicting (ie. damaging, neutral, and tolerated). Also, the nucleotide is very poorly conserved among 1000 vertebrates. In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Pendred Syndrome (no codes met; ClinGen Hearing Loss VCEP Specifications Version 2; 02/19/2025).
Not Met criteria codes
PS2
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
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
PP3
In-silico predictors are conflicting. REVEL score is not available.
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest MAF in gnomAD v4.0.0 is 0.03221 % (2/6022 alleles) in the Middle Eastern population (no population codes met). The next highest MAF in gnomAD is 0.0175 % (13/74302 alleles) in the African/African American population (doesn’t meet any population codes either).
BA1
The variant is present in 0.01% of African alleles and 0.007% of European (Non-Finnish) alleles in gnomAD
BS2
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
The variant is present in 0.01% of African alleles and 0.007% of European (Non-Finnish) alleles in gnomAD
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
BP4
In-silico predictors are conflicting. Nucleotide is very poorly conserved among 100 vertebrates. REVEL score is not available.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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