rs1126727

Positions:

• chr1-63629577-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002633.3(PGM1):​c.399T>C​(p.Ile133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,613,720 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (130 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (130 hom.)
• Consequence: PGM1 NM_002633.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00600

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-63629577-T-C is Benign according to our data. Variant chr1-63629577-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 297872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGM1	NM_002633.3	c.399T>C	p.Ile133=	synonymous_variant	2/11	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.453T>C	p.Ile151=	synonymous_variant	2/11		NP_001166289.1
PGM1	NM_001172819.2	c.-193T>C		5_prime_UTR_variant	2/11		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.399T>C	p.Ile133=	synonymous_variant	2/11	1	NM_002633.3	ENSP00000360125	P1
PGM1	ENST00000650546.1	c.399T>C	p.Ile133=	synonymous_variant	2/12			ENSP00000497812
PGM1	ENST00000371083.4	c.453T>C	p.Ile151=	synonymous_variant	2/11	2		ENSP00000360124
PGM1	ENST00000540265.5	c.-193T>C		5_prime_UTR_variant	2/11	2		ENSP00000443449

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3690 AN: 152110 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00617 AC: 1528 AN: 247762 Hom.: 56 AF XY: 0.00470 AC XY: 632 AN XY: 134514

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.00498

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000207

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00236 AC: 3444 AN: 1461492 Hom.: 130 Cov.: 32 AF XY: 0.00204 AC XY: 1483 AN XY: 727038

Gnomad4 AFR exome AF: 0.0819

Gnomad4 AMR exome AF: 0.00557

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000801

Gnomad4 OTH exome AF: 0.00553

GnomAD4 genome AF: 0.0243 AC: 3703 AN: 152228 Hom.: 130 Cov.: 32 AF XY: 0.0239 AC XY: 1777 AN XY: 74430

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00747 Hom.: 25

Bravo AF: 0.0276

Asia WGS AF: 0.00636 AC: 22 AN: 3476

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PGM1-congenital disorder of glycosylation Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.4
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs1126727; hg19: chr1-64095248;