1-63629539-G-T

Variant names:

• chr1-63629539-G-T
• rs398122912
• NM_002633.3:c.361G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001172819.2(PGM1):​c.-231G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGM1 NM_001172819.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.86
• Publications: 11 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]

PGM1 Gene-Disease associations (from GenCC):

• PGM1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172819.2. 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.361G>T	p.Gly121Trp	missense	Exon 2 of 11	NP_002624.2
	PGM1	NM_001172819.2		c.-231G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001166290.1	P36871-3
	PGM1	NM_001172818.1		c.415G>T	p.Gly139Trp	missense	Exon 2 of 11	NP_001166289.1	P36871-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	ENST00000371084.8	TSL:1 MANE Select	c.361G>T	p.Gly121Trp	missense	Exon 2 of 11	ENSP00000360125.3	P36871-1
	PGM1	ENST00000540265.5	TSL:2	c.-231G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000443449.1	P36871-3
	PGM1	ENST00000895883.1		c.361G>T	p.Gly121Trp	missense	Exon 2 of 12	ENSP00000565942.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248944 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Pathogenic	4.6	H
PhyloP100		9.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.77		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.90
MPC		0.66
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.99
gMVP		0.91
Mutation Taster		=155/145	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs398122912; hg19: chr1-64095210;