chr1-63593574-TCCAGAGCA-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002633.3(PGM1):c.87_94delCCAGAGCA(p.Phe29LeufsTer73) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_002633.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PGM1 | ENST00000371084.8 | c.87_94delCCAGAGCA | p.Phe29LeufsTer73 | frameshift_variant | Exon 1 of 11 | 1 | NM_002633.3 | ENSP00000360125.3 | ||
PGM1 | ENST00000650546.1 | c.87_94delCCAGAGCA | p.Phe29LeufsTer73 | frameshift_variant | Exon 1 of 12 | ENSP00000497812.1 | ||||
ITGB3BP | ENST00000478138.1 | n.140_147delTGCTCTGG | non_coding_transcript_exon_variant | Exon 1 of 5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249576Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135378
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461482Hom.: 0 AF XY: 0.00000825 AC XY: 6AN XY: 727062
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
PGM1-congenital disorder of glycosylation Pathogenic:1
Variant summary: PGM1 c.87_94delCCAGAGCA (p.Phe29LeufsX73) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic in ClinVar. The variant allele was found at a frequency of 8e-06 in 249576 control chromosomes (gnomAD). To our knowledge, no occurrence of c.87_94delCCAGAGCA in individuals affected with PGM1-Congenital Disorder Of Glycosylation and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at