NM_138691.3:c.339G>A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_138691.3(TMC1):c.339G>A(p.Met113Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000818 in 1,600,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_138691.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000597 AC: 9AN: 150764Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250494Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135422
GnomAD4 exome AF: 0.0000841 AC: 122AN: 1450178Hom.: 0 Cov.: 30 AF XY: 0.0000818 AC XY: 59AN XY: 721676
GnomAD4 genome AF: 0.0000597 AC: 9AN: 150764Hom.: 0 Cov.: 29 AF XY: 0.0000408 AC XY: 3AN XY: 73574
ClinVar
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 36 Uncertain:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not specified Uncertain:1
The p.Met113Ile variant in TMC1 has been previously reported by our laboratory i n one individual with sensorineural hearing loss and has been identified in 0.00 6% (7/126210) of European chromosomes by the Genome Aggregation Database (gnomAD , http://gnomad.broadinstitute.org). Computational prediction tools and conserva tion analysis do not provide strong support for or against an impact to the prot ein. In summary, the clinical significance of the p.Met113Ile variant is uncerta in. ACMG/AMP Criteria applied: PM2. -
not provided Uncertain:1
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -
Autosomal recessive nonsyndromic hearing loss 7 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at