rs35940413
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006031.6(PCNT):āc.5522A>Gā(p.Asn1841Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,612,692 control chromosomes in the GnomAD database, including 19,522 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.5522A>G | p.Asn1841Ser | missense_variant | 28/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.5168A>G | p.Asn1723Ser | missense_variant | 28/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.5522A>G | p.Asn1841Ser | missense_variant | 28/47 | 1 | NM_006031.6 | P2 | |
PCNT | ENST00000480896.5 | c.5168A>G | p.Asn1723Ser | missense_variant | 28/47 | 1 | A2 | ||
PCNT | ENST00000695558.1 | c.5555A>G | p.Asn1852Ser | missense_variant | 29/48 | A2 | |||
PCNT | ENST00000703224.1 | c.*4765A>G | 3_prime_UTR_variant, NMD_transcript_variant | 30/49 |
Frequencies
GnomAD3 genomes ? AF: 0.214 AC: 32584AN: 151970Hom.: 5447 Cov.: 33
GnomAD3 exomes AF: 0.133 AC: 32782AN: 247286Hom.: 3307 AF XY: 0.128 AC XY: 17288AN XY: 134712
GnomAD4 exome AF: 0.123 AC: 179693AN: 1460598Hom.: 14070 Cov.: 34 AF XY: 0.122 AC XY: 88755AN XY: 726638
GnomAD4 genome ? AF: 0.214 AC: 32621AN: 152094Hom.: 5452 Cov.: 33 AF XY: 0.209 AC XY: 15550AN XY: 74370
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 18, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 07, 2013 | - - |
PCNT-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 19, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Microcephalic osteodysplastic primordial dwarfism type II Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at