rs41291967
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000359794.11(PFKM):c.1500+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,612,842 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 76 hom., cov: 32)
Exomes 𝑓: 0.0065 ( 100 hom. )
Consequence
PFKM
ENST00000359794.11 intron
ENST00000359794.11 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.311
Genes affected
PFKM (HGNC:8877): (phosphofructokinase, muscle) Three phosphofructokinase isozymes exist in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Tetramer composition varies depending on tissue type. This gene encodes the muscle-type isozyme. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 12-48141859-C-T is Benign according to our data. Variant chr12-48141859-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0194 (2949/152242) while in subpopulation AFR AF= 0.0483 (2007/41540). AF 95% confidence interval is 0.0466. There are 76 homozygotes in gnomad4. There are 1502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 76 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PFKM | NM_000289.6 | c.1500+32C>T | intron_variant | ENST00000359794.11 | NP_000280.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PFKM | ENST00000359794.11 | c.1500+32C>T | intron_variant | 1 | NM_000289.6 | ENSP00000352842 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0192 AC: 2914AN: 152124Hom.: 70 Cov.: 32
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GnomAD3 exomes AF: 0.0109 AC: 2740AN: 251302Hom.: 43 AF XY: 0.00982 AC XY: 1334AN XY: 135828
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GnomAD4 exome AF: 0.00649 AC: 9475AN: 1460600Hom.: 100 Cov.: 31 AF XY: 0.00637 AC XY: 4626AN XY: 726710
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GnomAD4 genome AF: 0.0194 AC: 2949AN: 152242Hom.: 76 Cov.: 32 AF XY: 0.0202 AC XY: 1502AN XY: 74450
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2018 | 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Glycogen storage disease, type VII Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 19, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at