rs138631461
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001146079.2(CLDN14):c.337G>A(p.Ala113Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001146079.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLDN14 | NM_001146079.2 | c.337G>A | p.Ala113Thr | missense_variant | 2/2 | ENST00000399135.6 | NP_001139551.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLDN14 | ENST00000399135.6 | c.337G>A | p.Ala113Thr | missense_variant | 2/2 | 1 | NM_001146079.2 | ENSP00000382087.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246328Hom.: 0 AF XY: 0.00000750 AC XY: 1AN XY: 133422
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460860Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 726742
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 10, 2017 | The p.Ala113Thr variant in CLDN14 has not been previously reported in individual s with hearing loss, but has been identified in 1/15172 African and in 1/107834 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org; dbSNP rs138631461). Although this variant has been seen in t he general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that thi s variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p .Ala113Thr variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at