rs111033463
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033056.4(PCDH15):c.5398G>A(p.Val1800Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000947 in 1,597,250 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_033056.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.5398G>A | p.Val1800Ile | missense_variant | Exon 33 of 33 | 1 | NM_033056.4 | ENSP00000322604.6 | ||
PCDH15 | ENST00000644397.2 | c.4368-2098G>A | intron_variant | Intron 32 of 37 | NM_001384140.1 | ENSP00000495195.1 |
Frequencies
GnomAD3 genomes AF: 0.000702 AC: 105AN: 149500Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00138 AC: 304AN: 221008Hom.: 3 AF XY: 0.00177 AC XY: 211AN XY: 119246
GnomAD4 exome AF: 0.000972 AC: 1407AN: 1447634Hom.: 14 Cov.: 32 AF XY: 0.00124 AC XY: 892AN XY: 718994
GnomAD4 genome AF: 0.000702 AC: 105AN: 149616Hom.: 1 Cov.: 32 AF XY: 0.000701 AC XY: 51AN XY: 72780
ClinVar
Submissions by phenotype
not provided Benign:6
- -
- -
This variant is associated with the following publications: (PMID: 27984600, 22135276) -
- -
- -
- -
not specified Benign:2
Val1800Ile in exon 33 of PCDH15: This variant is not expected to have clinical s ignificance because it has been identified in 0.7% (94/13018) of South Asian chr omosomes, including 1 homozygote, by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org; dbSNP rs111033463). In addition, the valine (Val) residue at position 1800 is not conserved in several species, with chimpanzee an d macaque having an isoleucine (Ile) at this position. -
- -
Usher syndrome type 1F Benign:2
- -
- -
Usher syndrome type 1D;C1836027:Autosomal recessive nonsyndromic hearing loss 23;C1865885:Usher syndrome type 1F Benign:1
- -
PCDH15-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Usher syndrome type 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at