rs752254649
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_005422.4(TECTA):c.1123G>A(p.Val375Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,613,948 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_005422.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.1123G>A | p.Val375Ile | missense_variant | Exon 7 of 24 | 5 | NM_005422.4 | ENSP00000376543.1 | ||
TECTA | ENST00000264037.2 | c.1123G>A | p.Val375Ile | missense_variant | Exon 6 of 23 | 1 | ENSP00000264037.2 | |||
TECTA | ENST00000642222.1 | c.1123G>A | p.Val375Ile | missense_variant | Exon 7 of 24 | ENSP00000493855.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251444Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135902
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461834Hom.: 0 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727222
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74304
ClinVar
Submissions by phenotype
not specified Uncertain:1
p.Val375Ile, c.1123G>A (TECTA; NM_005422.2; Chr11g.120989347G>A; GRCh37): The p. Val375Ile variant in TECTA has not been previously reported in individuals with hearing loss, but has been identified in 8/126686 of European chromosomes and 2/ 30782 of South Asian chromosomes by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org; dbSNP 752254649). Although this variant has been seen in the general population, its frequency is not high enough to rule out a p athogenic role. Computational prediction tools and conservation analysis suggest that the p.Val375Ile variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical sign ificance of the p.Val375Ile variant is uncertain. ACMG/AMP Criteria applied: PM2 ; PP3 -
Hearing impairment Uncertain:1
PM2_Moderate, PP2_Supporting -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at