rs139915181
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033056.4(PCDH15):āc.4733T>Cā(p.Val1578Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000274 in 1,613,942 control chromosomes in the GnomAD database, including 3 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 (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Synonymous variant affecting the same amino acid position (i.e. V1578V) 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.4733T>C | p.Val1578Ala | missense_variant | 33/33 | ENST00000320301.11 | |
PCDH15 | NM_001384140.1 | c.4368-2763T>C | intron_variant | ENST00000644397.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.4733T>C | p.Val1578Ala | missense_variant | 33/33 | 1 | NM_033056.4 | ||
PCDH15 | ENST00000644397.2 | c.4368-2763T>C | intron_variant | NM_001384140.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00156 AC: 237AN: 152036Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000310 AC: 78AN: 251366Hom.: 0 AF XY: 0.000272 AC XY: 37AN XY: 135858
GnomAD4 exome AF: 0.000140 AC: 204AN: 1461788Hom.: 1 Cov.: 33 AF XY: 0.000121 AC XY: 88AN XY: 727200
GnomAD4 genome ? AF: 0.00156 AC: 238AN: 152154Hom.: 2 Cov.: 32 AF XY: 0.00129 AC XY: 96AN XY: 74404
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 14, 2017 | The c.4733T>C; p.Val1578Ala variant (rs139915181) has not been reported in the medical literature, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.5 percent in the African population (identified on 122 out of 24,028 chromosomes), and reported to ClinVar as likely benign (Variation ID: 178520). The valine at position 1578 is weakly conserved considering 12 species (Alamut v2.9.0) and computational analyses of the p.Val1578Ala variant on protein structure and function indicate a neutral effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Altogether the p.Val1578Ala variant is likely to be benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Val1578Ala in Exon 33 of PCDH15: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (13/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs139915181). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at