rs191736346
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_033056.4(PCDH15):c.5603C>T(p.Thr1868Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,597,172 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_033056.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.5603C>T | p.Thr1868Met | missense_variant | 33/33 | ENST00000320301.11 | NP_149045.3 | |
PCDH15 | NM_001384140.1 | c.4368-1893C>T | intron_variant | ENST00000644397.2 | NP_001371069.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.5603C>T | p.Thr1868Met | missense_variant | 33/33 | 1 | NM_033056.4 | ENSP00000322604 | ||
PCDH15 | ENST00000644397.2 | c.4368-1893C>T | intron_variant | NM_001384140.1 | ENSP00000495195 |
Frequencies
GnomAD3 genomes AF: 0.00386 AC: 558AN: 144618Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.000978 AC: 246AN: 251408Hom.: 3 AF XY: 0.000670 AC XY: 91AN XY: 135874
GnomAD4 exome AF: 0.000383 AC: 556AN: 1452480Hom.: 2 Cov.: 32 AF XY: 0.000321 AC XY: 232AN XY: 723090
GnomAD4 genome AF: 0.00386 AC: 559AN: 144692Hom.: 3 Cov.: 32 AF XY: 0.00363 AC XY: 257AN XY: 70794
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 13, 2017 | Thr1868Met in exon 33 of PCDH15: This variant is not expected to have clinical s ignificance because it has been identified in 1.5% (132/8652) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs191736346). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 09, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 14, 2018 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2019 | This variant is associated with the following publications: (PMID: 26969326) - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at