rs61735823
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_006031.6(PCNT):c.506G>A(p.Arg169His) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R169C) 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 Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.506G>A | p.Arg169His | missense_variant | 3/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.152G>A | p.Arg51His | missense_variant | 3/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.506G>A | p.Arg169His | missense_variant | 3/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 43AN: 137968Hom.: 0 Cov.: 33 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000503 AC: 72AN: 1430710Hom.: 0 Cov.: 33 AF XY: 0.0000646 AC XY: 46AN XY: 711552
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000311 AC: 43AN: 138084Hom.: 0 Cov.: 33 AF XY: 0.000325 AC XY: 22AN XY: 67626
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 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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2020 | This variant is associated with the following publications: (PMID: 29778030) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at