rs114468011
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_005609.4(PYGM):c.848A>G(p.Asn283Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,613,688 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts 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. N283N) has been classified as Likely benign.
Frequency
Consequence
NM_005609.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGM | NM_005609.4 | c.848A>G | p.Asn283Ser | missense_variant | 7/20 | ENST00000164139.4 | |
PYGM | NM_001164716.1 | c.584A>G | p.Asn195Ser | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGM | ENST00000164139.4 | c.848A>G | p.Asn283Ser | missense_variant | 7/20 | 1 | NM_005609.4 | P1 | |
PYGM | ENST00000377432.7 | c.584A>G | p.Asn195Ser | missense_variant | 5/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000809 AC: 123AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00133 AC: 334AN: 251388Hom.: 4 AF XY: 0.00142 AC XY: 193AN XY: 135888
GnomAD4 exome AF: 0.00121 AC: 1769AN: 1461448Hom.: 6 Cov.: 32 AF XY: 0.00125 AC XY: 910AN XY: 727052
GnomAD4 genome ? AF: 0.000808 AC: 123AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.000833 AC XY: 62AN XY: 74420
ClinVar
Submissions by phenotype
Glycogen storage disease, type V Uncertain:2Benign:3
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
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 provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | PYGM: BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 09, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Dec 05, 2022 | BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2019 | - - |
PYGM-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 08, 2020 | 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