chr1-63631749-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002633.3(PGM1):c.649C>T(p.Arg217Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002633.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGM1 | NM_002633.3 | c.649C>T | p.Arg217Ter | stop_gained | 4/11 | ENST00000371084.8 | |
PGM1 | NM_001172818.1 | c.703C>T | p.Arg235Ter | stop_gained | 4/11 | ||
PGM1 | NM_001172819.2 | c.58C>T | p.Arg20Ter | stop_gained | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGM1 | ENST00000371084.8 | c.649C>T | p.Arg217Ter | stop_gained | 4/11 | 1 | NM_002633.3 | P1 | |
PGM1 | ENST00000650546.1 | c.649C>T | p.Arg217Ter | stop_gained | 4/12 | ||||
PGM1 | ENST00000371083.4 | c.703C>T | p.Arg235Ter | stop_gained | 4/11 | 2 | |||
PGM1 | ENST00000540265.5 | c.58C>T | p.Arg20Ter | stop_gained | 4/11 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251096Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135686
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461358Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727020
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 12, 2017 | - - |
PGM1-congenital disorder of glycosylation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2023 | This sequence change creates a premature translational stop signal (p.Arg217*) in the PGM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PGM1 are known to be pathogenic (PMID: 22492991). This variant is present in population databases (rs770066171, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PGM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 499573). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at