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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_005422.2(TECTA):c.3097C>T (p.Arg1033Trp)

CA182517

178538 (ClinVar)

Gene: TECTA
Condition: nonsyndromic genetic deafness
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7d1da592-1e07-4180-b86b-6fdeb5ee5521
Approved on: 2019-04-29
Published on: 2019-07-17

HGVS expressions

NM_005422.2:c.3097C>T
NM_005422.2(TECTA):c.3097C>T (p.Arg1033Trp)
NM_005422.2:n.3097C>T
ENST00000264037.2:n.3097C>T
ENST00000392793.5:c.3097C>T
NC_000011.10:g.121137576C>T
CM000673.2:g.121137576C>T
NC_000011.9:g.121008285C>T
CM000673.1:g.121008285C>T
NC_000011.8:g.120513495C>T
NG_011633.1:g.39911C>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 1
BS1
Not Met criteria codes 12
BA1 PM5 PM4 PM3 PM2 BP4 BP3 BP2 PVS1 BP7 PS1 PP3

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The filtering allele frequency (the lower threshold of the 95% CI of 88/24956) of the p.Arg1033Trp variant in the TECTA gene is 0.29% for African chromosomes by gnomAD, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). The p.Arg1033Trp variant has been identified in one hearing loss patient who carries a second TECTA variant, p.Gln234Arg, that has previously been classified as likely benign by the HL VCEP (PMID 26969326, SCV000840522.3). The variant has also been observed by Partners LMM in one homozygous patient, two heterozygous patients, and two compound heterozygous patients who also carry one or two pathogenic or VUS favor-pathogenic variants. These cases are inconclusive (SCV000204966.4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1.
Met criteria codes
BS1
The MAF is 0.29% (88/24956 African alleles)
Not Met criteria codes
BA1
The MAF is 0.29% (88/24956 African alleles)
PM5
p.Arg1033Gln has been reported before (Yamamoto 2017) but has not been assessed in ClinVar or by the HL VCEP.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Patient 369 carries the p.Arg1033Trp variant in heterozygosity, as well as a heterozygous c.701A>G p.Gln234Arg TECTA variant. The p.Gln234Arg variant is present in 112/24924 (0.45%) African alleles in gnomad and has been classified as likely benign by the HL VCEP. This patient has sporadic, mild-moderate, symmetric, childhood onset hearing loss. PubMed:26969326
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
REVEL score is 0.552 which is above the benign cut off score of 0.15
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
Patient 369 carries the p.Arg1033Trp variant in heterozygosity, as well as a heterozygous c.701A>G p.Gln234Arg TECTA variant. The p.Gln234Arg variant is present in 112/24924 (0.45%) African alleles in gnomad and has been classified as likely benign by the HL VCEP. This patient has sporadic, mild-moderate, symmetric, childhood onset hearing loss. PubMed:26969326
PVS1
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL score is 0.552 which is below the pathogenic cut off score of 0.7
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.