chr1-63648516-G-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_002633.3(PGM1):​c.1145-1G>C variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

PGM1
NM_002633.3 splice_acceptor, intron

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.96
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-63648516-G-C is Pathogenic according to our data. Variant chr1-63648516-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 13651.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PGM1NM_002633.3 linkc.1145-1G>C splice_acceptor_variant, intron_variant ENST00000371084.8 NP_002624.2 P36871-1
PGM1NM_001172818.1 linkc.1199-1G>C splice_acceptor_variant, intron_variant NP_001166289.1 P36871-2B7Z6C2
PGM1NM_001172819.2 linkc.554-1G>C splice_acceptor_variant, intron_variant NP_001166290.1 P36871-3B4DDQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PGM1ENST00000371084.8 linkc.1145-1G>C splice_acceptor_variant, intron_variant 1 NM_002633.3 ENSP00000360125.3 P36871-1
PGM1ENST00000650546.1 linkc.1145-1G>C splice_acceptor_variant, intron_variant ENSP00000497812.1 A0A3B3ITK7
PGM1ENST00000371083.4 linkc.1199-1G>C splice_acceptor_variant, intron_variant 2 ENSP00000360124.4 P36871-2
PGM1ENST00000540265.5 linkc.554-1G>C splice_acceptor_variant, intron_variant 2 ENSP00000443449.1 P36871-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

PGM1-congenital disorder of glycosylation Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJul 23, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
33
DANN
Uncertain
0.99
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
GERP RS
6.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.95
SpliceAI score (max)
0.95
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.36
Position offset: -49
DS_AL_spliceai
0.95
Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587776801; hg19: chr1-64114187; API