rs587777564
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015599.3(PGM3):c.737_738insA(p.Asn246LysfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
PGM3
NM_015599.3 frameshift
NM_015599.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-83181785-A-AT is Pathogenic according to our data. Variant chr6-83181785-A-AT is described in ClinVar as [Pathogenic]. Clinvar id is 140734.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGM3 | NM_015599.3 | c.737_738insA | p.Asn246LysfsTer7 | frameshift_variant | 6/13 | ENST00000513973.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGM3 | ENST00000513973.6 | c.737_738insA | p.Asn246LysfsTer7 | frameshift_variant | 6/13 | 1 | NM_015599.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Immunodeficiency 23 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Jul 03, 2014 | segregates with the phenotype in an affected family - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 03, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at