chr15-43600227-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_153700.2(STRC):c.5060C>A(p.Ala1687Asp) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_153700.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 4AN: 144660Hom.: 0 Cov.: 23 FAILED QC
GnomAD4 exome AF: 0.0000177 AC: 21AN: 1187704Hom.: 0 Cov.: 17 AF XY: 0.0000168 AC XY: 10AN XY: 595412
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000277 AC: 4AN: 144660Hom.: 0 Cov.: 23 AF XY: 0.0000143 AC XY: 1AN XY: 70046
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 16 Uncertain:1
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Deafness, autosomal recessive 16 (MIM#603720). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to aspartic acid. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (v3 filtered out: 4 heterozygotes, 0 homozygotes). (SP) 0309 - Alternative amino acid changes at the same position have been observed in gnomAD (v2 highest count: 1 heterozygote, 0 homozygote). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. The p.(Ala1687Gly) and p.(Ala1687Thr) variants are both listed in the Deafness Variation Database as VUSs based on in silico predictions, however no clinical information was provided. (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant was listed in the Deafness Variation Database as pathogenic. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1201 - Heterozygous variant inferred to be in trans with a pathogenic heterozygous deletion in a recessive disease. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at