10-54023022-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_033056.4(PCDH15):c.2396G>A(p.Arg799His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R799R) has been classified as Likely benign.
Frequency
Consequence
NM_033056.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.2396G>A | p.Arg799His | missense_variant | 19/33 | ENST00000320301.11 | |
PCDH15 | NM_001384140.1 | c.2396G>A | p.Arg799His | missense_variant | 19/38 | ENST00000644397.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.2396G>A | p.Arg799His | missense_variant | 19/33 | 1 | NM_033056.4 | ||
PCDH15 | ENST00000644397.2 | c.2396G>A | p.Arg799His | missense_variant | 19/38 | NM_001384140.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251304Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135806
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461750Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727172
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74282
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 | Feb 26, 2015 | The p.Arg799His variant in PCDH15 has not been previously reported in individual s with Usher syndrome. This variant has been identified in 1/10402 African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs199824864). Computational prediction tools and conservation analyses d o not provide strong support for or against an impact to the protein. In summary , the clinical significance of the p.Arg799His variant is uncertain. - |
Usher syndrome type 1F Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 799 of the PCDH15 protein (p.Arg799His). This variant is present in population databases (rs199824864, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 229137). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at