11-121118393-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_005422.4(TECTA):c.878A>G(p.Tyr293Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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 -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.878A>G | p.Tyr293Cys | missense_variant | Exon 7 of 24 | 5 | NM_005422.4 | ENSP00000376543.1 | ||
TECTA | ENST00000264037.2 | c.878A>G | p.Tyr293Cys | missense_variant | Exon 6 of 23 | 1 | ENSP00000264037.2 | |||
TECTA | ENST00000642222.1 | c.878A>G | p.Tyr293Cys | missense_variant | Exon 7 of 24 | ENSP00000493855.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251422Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727220
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74488
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Tyr293Cys variant in TECTA has not been previously reported in individuals with hearing loss, but has been identified in 7/33582 of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs185351501). Although this variant has been seen in the general population, i ts frequency is not high enough to rule out a pathogenic role. Computational pr ediction tools and conservation analyses suggest that this variant may not impac t the protein, though this information is not predictive enough to rule out path ogenicity. In summary, the clinical significance of the p.Tyr293Cys variant is u ncertain. -
Inborn genetic diseases Uncertain:1
The c.878A>G (p.Y293C) alteration is located in exon 6 (coding exon 6) of the TECTA gene. This alteration results from a A to G substitution at nucleotide position 878, causing the tyrosine (Y) at amino acid position 293 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21520338, 31554319, 9590290) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at