rs11004439
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_033056.4(PCDH15):āc.55T>Gā(p.Ser19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,610,862 control chromosomes in the GnomAD database, including 44,316 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 Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S19T) 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.55T>G | p.Ser19Ala | missense_variant | 2/33 | ENST00000320301.11 | NP_149045.3 | |
PCDH15 | NM_001384140.1 | c.55T>G | p.Ser19Ala | missense_variant | 2/38 | ENST00000644397.2 | NP_001371069.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.55T>G | p.Ser19Ala | missense_variant | 2/33 | 1 | NM_033056.4 | ENSP00000322604 | ||
PCDH15 | ENST00000644397.2 | c.55T>G | p.Ser19Ala | missense_variant | 2/38 | NM_001384140.1 | ENSP00000495195 |
Frequencies
GnomAD3 genomes AF: 0.204 AC: 31001AN: 151808Hom.: 3424 Cov.: 31
GnomAD3 exomes AF: 0.221 AC: 55151AN: 250098Hom.: 6698 AF XY: 0.218 AC XY: 29415AN XY: 135170
GnomAD4 exome AF: 0.232 AC: 338249AN: 1458936Hom.: 40894 Cov.: 33 AF XY: 0.230 AC XY: 167052AN XY: 725862
GnomAD4 genome AF: 0.204 AC: 31010AN: 151926Hom.: 3422 Cov.: 31 AF XY: 0.199 AC XY: 14783AN XY: 74290
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 23, 2009 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 25, 2016 | Variant summary: The PCDH15 c.55T>G variant affects a non-conserved nucleotide, resulting in amino acid change from Ser to Ala. 3/4 in-silico tools predict benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 25808/118352 control chromosomes (3055 homozygotes) at a frequency of 0.2180614, which is about 69 times of the maximal expected frequency of a pathogenic PCDH15 allele (0.0031623), suggesting this variant is a benign polymorphism. This variant is reported in USH patients without evidence for causality and authors listed the variant as a frequent SNP. In addition, one reputable clinical laboratory via ClinVar classified this variant as benign. Taken together, this variant was classified as Benign. - |
Usher syndrome type 1F Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Autosomal recessive nonsyndromic hearing loss 23 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Usher syndrome type 1 Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at