chr10-53806748-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001384140.1(PCDH15):āc.5054T>Cā(p.Val1685Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001384140.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH15 | NM_001384140.1 | c.5054T>C | p.Val1685Ala | missense_variant | 38/38 | ENST00000644397.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000644397.2 | c.5054T>C | p.Val1685Ala | missense_variant | 38/38 | NM_001384140.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248692Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135118
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461634Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727100
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74264
ClinVar
Submissions by phenotype
Usher syndrome type 1F Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 26, 2017 | - - |
Uncertain significance, criteria provided, single submitter | curation | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Jan 24, 2023 | The p.Val1685Ala variant in PCDH15 has been reported in 1 individual, in the homozygous state, with Usher syndrome type 1F (PMID: 22952768) and has been identified in 0.008% (3/35362) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs140716525). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 554592) and has been interpreted as a variant of uncertain significance by Counsyl. Computational prediction tools, including splice predictors, and conservation analyses suggest that this 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.Val1685Ala variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PM3_supporting, BP4 (Richards 2015). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at