rs141635334
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_006031.6(PCNT):c.6761G>A(p.Cys2254Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,565,204 control chromosomes in the GnomAD database, including 12 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C2254F) has been classified as Uncertain significance.
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.6761G>A | p.Cys2254Tyr | missense_variant | 30/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.6407G>A | p.Cys2136Tyr | missense_variant | 30/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.6761G>A | p.Cys2254Tyr | missense_variant | 30/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000802 AC: 122AN: 152174Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00112 AC: 233AN: 207318Hom.: 5 AF XY: 0.00115 AC XY: 128AN XY: 111264
GnomAD4 exome AF: 0.000641 AC: 906AN: 1413030Hom.: 10 Cov.: 34 AF XY: 0.000651 AC XY: 454AN XY: 697394
GnomAD4 genome ? AF: 0.000802 AC: 122AN: 152174Hom.: 2 Cov.: 32 AF XY: 0.000753 AC XY: 56AN XY: 74340
ClinVar
Submissions by phenotype
Microcephalic osteodysplastic primordial dwarfism type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 26, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at