rs146745502
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033056.4(PCDH15):āc.4334C>Gā(p.Ala1445Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,613,180 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. A1445A) has been classified as Likely benign.
Frequency
Consequence
NM_033056.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.4334C>G | p.Ala1445Gly | missense_variant | 32/33 | ENST00000320301.11 | |
PCDH15 | NM_001384140.1 | c.4334C>G | p.Ala1445Gly | missense_variant | 32/38 | ENST00000644397.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.4334C>G | p.Ala1445Gly | missense_variant | 32/33 | 1 | NM_033056.4 | ||
PCDH15 | ENST00000644397.2 | c.4334C>G | p.Ala1445Gly | missense_variant | 32/38 | NM_001384140.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000644 AC: 98AN: 152220Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00267 AC: 663AN: 248074Hom.: 12 AF XY: 0.00194 AC XY: 261AN XY: 134408
GnomAD4 exome AF: 0.000534 AC: 780AN: 1460842Hom.: 11 Cov.: 31 AF XY: 0.000447 AC XY: 325AN XY: 726582
GnomAD4 genome ? AF: 0.000643 AC: 98AN: 152338Hom.: 2 Cov.: 32 AF XY: 0.000483 AC XY: 36AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 26, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 04, 2016 | p.Ala1445Gly in exon 32 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 2.3% (261/11556) of Latino chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs146745502). - |
PCDH15-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Usher syndrome type 1F Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Usher syndrome type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at