chr1-63593512-GACCCAGGCGT-G
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002633.3(PGM1):c.28_37delCAGGCGTACC(p.Gln10ArgfsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
PGM1
NM_002633.3 frameshift
NM_002633.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.66
Publications
0 publications found
Genes affected
PGM1 (HGNC:8905): (phosphoglucomutase 1) The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red cells, PGM2 is a major isozyme. This gene is highly polymorphic. Mutations in this gene cause glycogen storage disease type 14. Alternativley spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Mar 2010]
ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 42 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-63593512-GACCCAGGCGT-G is Pathogenic according to our data. Variant chr1-63593512-GACCCAGGCGT-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1694516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002633.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PGM1 | NM_002633.3 | MANE Select | c.28_37delCAGGCGTACC | p.Gln10ArgfsTer14 | frameshift | Exon 1 of 11 | NP_002624.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PGM1 | ENST00000371084.8 | TSL:1 MANE Select | c.28_37delCAGGCGTACC | p.Gln10ArgfsTer14 | frameshift | Exon 1 of 11 | ENSP00000360125.3 | P36871-1 | |
| PGM1 | ENST00000895883.1 | c.28_37delCAGGCGTACC | p.Gln10ArgfsTer14 | frameshift | Exon 1 of 12 | ENSP00000565942.1 | |||
| PGM1 | ENST00000650546.1 | c.28_37delCAGGCGTACC | p.Gln10ArgfsTer14 | frameshift | Exon 1 of 12 | ENSP00000497812.1 | A0A3B3ITK7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249570 AF XY: 0.00000739 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249570
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461558Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727098 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1461558
Hom.:
AF XY:
AC XY:
3
AN XY:
727098
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53236
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1111908
Other (OTH)
AF:
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.433
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
1
-
-
PGM1-congenital disorder of glycosylation (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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