rs2228500
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000289.6(PFKM):c.299G>A(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,613,792 control chromosomes in the GnomAD database, including 34,053 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 Likely benign (★★).
Frequency
Consequence
NM_000289.6 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PFKM | NM_000289.6 | c.299G>A | p.Arg100Gln | missense_variant | Exon 5 of 23 | ENST00000359794.11 | NP_000280.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.166 AC: 25223AN: 151988Hom.: 2440 Cov.: 32
GnomAD3 exomes AF: 0.178 AC: 44734AN: 251114Hom.: 4418 AF XY: 0.182 AC XY: 24696AN XY: 135714
GnomAD4 exome AF: 0.204 AC: 298112AN: 1461686Hom.: 31611 Cov.: 36 AF XY: 0.203 AC XY: 147325AN XY: 727170
GnomAD4 genome AF: 0.166 AC: 25225AN: 152106Hom.: 2442 Cov.: 32 AF XY: 0.163 AC XY: 12085AN XY: 74364
ClinVar
Submissions by phenotype
Glycogen storage disease, type VII Benign:6
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. -
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This variant is interpreted as a Benign - Stand Alone, for Glycogen storage disease VII, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 =>Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
not specified Benign:4
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. -
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not provided Benign:2
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at