rs146728385
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006031.6(PCNT):c.2866G>A(p.Asp956Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.2866G>A | p.Asp956Asn | missense_variant | 15/47 | ENST00000359568.10 | NP_006022.3 | |
PCNT | NM_001315529.2 | c.2512G>A | p.Asp838Asn | missense_variant | 15/47 | NP_001302458.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.2866G>A | p.Asp956Asn | missense_variant | 15/47 | 1 | NM_006031.6 | ENSP00000352572.5 |
Frequencies
GnomAD3 genomes AF: 0.000506 AC: 77AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251116Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135848
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461646Hom.: 0 Cov.: 69 AF XY: 0.0000495 AC XY: 36AN XY: 727128
GnomAD4 genome AF: 0.000505 AC: 77AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38AN XY: 74508
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 22, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 956 of the PCNT protein (p.Asp956Asn). This variant is present in population databases (rs146728385, gnomAD 0.2%). 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: 211851). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 24, 2015 | - - |
Microcephalic osteodysplastic primordial dwarfism type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 22, 2024 | - - |
PCNT-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 04, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at