5-141945469-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016580.4(PCDH12):c.3467C>T(p.Ser1156Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S1156S) has been classified as Likely benign.
Frequency
Consequence
NM_016580.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH12 | NM_016580.4 | c.3467C>T | p.Ser1156Leu | missense_variant | 4/4 | ENST00000231484.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH12 | ENST00000231484.4 | c.3467C>T | p.Ser1156Leu | missense_variant | 4/4 | 1 | NM_016580.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 65
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1156 of the PCDH12 protein (p.Ser1156Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCDH12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1364964). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PCDH12 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at