rs546562229
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_006031.6(PCNT):c.4838C>T(p.Ala1613Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A1613A) has been classified as Likely benign.
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.4838C>T | p.Ala1613Val | missense_variant | 26/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.4484C>T | p.Ala1495Val | missense_variant | 26/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.4838C>T | p.Ala1613Val | missense_variant | 26/47 | 1 | NM_006031.6 | P2 | |
PCNT | ENST00000480896.5 | c.4484C>T | p.Ala1495Val | missense_variant | 26/47 | 1 | A2 | ||
PCNT | ENST00000695558.1 | c.4871C>T | p.Ala1624Val | missense_variant | 27/48 | A2 | |||
PCNT | ENST00000703224.1 | c.*4081C>T | 3_prime_UTR_variant, NMD_transcript_variant | 28/49 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 151960Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000279 AC: 70AN: 251310Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135846
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461656Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 727142
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 14, 2015 | - - |
Microcephalic osteodysplastic primordial dwarfism type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
PCNT-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 10, 2022 | 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at