rs6676290

chr1-63654368-G-Achr1-63654368-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002633.3(PGM1):c.1501G>A(p.Val501Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00876 in 1,613,858 control chromosomes in the GnomAD database, including 1,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (563 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (488 hom.)
• Consequence: PGM1 NM_002633.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.30

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012457967).
• BP6: Variant 1-63654368-G-A is Benign according to our data. Variant chr1-63654368-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 297892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM1	NM_002633.3	c.1501G>A	p.Val501Ile	missense_variant	10/11	ENST00000371084.8
PGM1	NM_001172818.1	c.1555G>A	p.Val519Ile	missense_variant	10/11
PGM1	NM_001172819.2	c.910G>A	p.Val304Ile	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM1	ENST00000371084.8	c.1501G>A	p.Val501Ile	missense_variant	10/11	1	NM_002633.3	P1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7015 AN: 152112 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0122 AC: 3062 AN: 251194 Hom.: 201 AF XY: 0.00901 AC XY: 1223 AN XY: 135756

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.00807

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00484 AC: 7075 AN: 1461630 Hom.: 488 Cov.: 32 AF XY: 0.00427 AC XY: 3103 AN XY: 727128

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.00888

Gnomad4 ASJ exome AF: 0.00379

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000321

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0464 AC: 7056 AN: 152228 Hom.: 563 Cov.: 32 AF XY: 0.0449 AC XY: 3341 AN XY: 74442

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.00727 Hom.: 177

Bravo AF: 0.0515

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.147 AC: 647

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0152 AC: 1840

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PGM1-congenital disorder of glycosylation Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 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

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Mar 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	19
Dann	Benign	0.79
DEOGEN2	Benign	0.36	T;.;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.69	T;T;T;T
MetaRNN	Benign	0.0012	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N;.;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.24	N;.;N;N
REVEL	Benign	0.055
Sift	Benign	0.84	T;.;T;T
Sift4G	Benign	0.67	T;.;T;T
Polyphen		0.0070	B;.;.;B
Vest4		0.070
MPC		0.14
ClinPred		0.015	T
GERP RS		4.3
Varity_R		0.098
gMVP		0.23

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: rs6676290; hg19: chr1-64120039;