chr11-121113198-G-C
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4
The NM_005422.4(TECTA):c.613G>C(p.Val205Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,940 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
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.613G>C | p.Val205Leu | missense_variant | Exon 5 of 24 | 5 | NM_005422.4 | ENSP00000376543.1 | ||
TECTA | ENST00000264037.2 | c.613G>C | p.Val205Leu | missense_variant | Exon 4 of 23 | 1 | ENSP00000264037.2 | |||
TECTA | ENST00000642222.1 | c.613G>C | p.Val205Leu | missense_variant | Exon 5 of 24 | ENSP00000493855.1 | ||||
TBCEL-TECTA | ENST00000645041.1 | c.*90G>C | downstream_gene_variant | ENSP00000496315.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152118Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000239 AC: 6AN: 251146 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727196 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74298 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Val205Leu variant in TECTA has not been previously reported in individuals with hearing loss, but has been identified in 2/19024 of chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3751076 47). Computational prediction tools and conservation analysis suggest that the p.Val205Leu variant may not impact the protein, though this information is not p redictive enough to rule out pathogenicity. In summary, the clinical significa nce of the p.Val205Leu variant is uncertain. -
Inborn genetic diseases Uncertain:1
The c.613G>C (p.V205L) alteration is located in exon 4 (coding exon 4) of the TECTA gene. This alteration results from a G to C substitution at nucleotide position 613, causing the valine (V) at amino acid position 205 to be replaced by a leucine (L). 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