rs201176638
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006031.6(PCNT):c.427C>T(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,598,784 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143H) has been classified as Uncertain significance.
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.427C>T | p.Arg143Cys | missense_variant | 3/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.73C>T | p.Arg25Cys | missense_variant | 3/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.427C>T | p.Arg143Cys | missense_variant | 3/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000224 AC: 34AN: 151920Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000203 AC: 51AN: 251442Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135894
GnomAD4 exome AF: 0.000281 AC: 406AN: 1446864Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 203AN XY: 719604
GnomAD4 genome ? AF: 0.000224 AC: 34AN: 151920Hom.: 0 Cov.: 34 AF XY: 0.000162 AC XY: 12AN XY: 74202
ClinVar
Submissions by phenotype
Microcephalic osteodysplastic primordial dwarfism type II Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 16, 2014 | - - |
PCNT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 20, 2024 | The PCNT c.427C>T variant is predicted to result in the amino acid substitution p.Arg143Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.076% of alleles in individuals of Latino descent in gnomAD. Of note, a different variant impacting the same amino acid residue (p.Arg143His) has been reported as de novo in at least one patient with autism (Family ID 13863 in Supplemental Table 2, Iossifov. 2014. PubMed ID: 25363768; Table S2, Turner et al. 2019. PubMed ID: 31785789). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 143 of the PCNT protein (p.Arg143Cys). This variant is present in population databases (rs201176638, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 159598). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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