rs855314

Variant names:

• chr1-63629440-A-G
• rs855314
• NM_002633.3:c.262A>G

Variant summary

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

The NM_001172819.2(PGM1):​c.-330A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,611,504 control chromosomes in the GnomAD database, including 17,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2331 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15467 hom.)
• Consequence: PGM1 NM_001172819.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 9.20

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=0.002285391).
• BP6: Variant 1-63629440-A-G is Benign according to our data. Variant chr1-63629440-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 297871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-63629440-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.262A>G	p.Ile88Val	missense_variant	Exon 2 of 11	ENST00000371084.8	NP_002624.2
PGM1	NM_001172819.2	c.-330A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11		NP_001166290.1
PGM1	NM_001172818.1	c.316A>G	p.Ile106Val	missense_variant	Exon 2 of 11		NP_001166289.1
PGM1	NM_001172819.2	c.-330A>G		5_prime_UTR_variant	Exon 2 of 11		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.262A>G	p.Ile88Val	missense_variant	Exon 2 of 11	1	NM_002633.3	ENSP00000360125.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24762 AN: 151950 Hom.: 2322 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.0907

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.125 AC: 31190 AN: 248928 Hom.: 2370 AF XY: 0.125 AC XY: 16855 AN XY: 134720

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.0696

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.00718

Gnomad SAS exome AF: 0.0948

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.140 AC: 204850 AN: 1459436 Hom.: 15467 Cov.: 32 AF XY: 0.139 AC XY: 101033 AN XY: 726132

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.0745

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.00428

Gnomad4 SAS exome AF: 0.0986

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.163 AC: 24806 AN: 152068 Hom.: 2331 Cov.: 32 AF XY: 0.160 AC XY: 11904 AN XY: 74318

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00908

Gnomad4 SAS AF: 0.0908

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.170

Alfa AF: 0.147 Hom.: 3656

Bravo AF: 0.164

TwinsUK AF: 0.149 AC: 553

ALSPAC AF: 0.147 AC: 567

ESP6500AA AF: 0.240 AC: 1057

ESP6500EA AF: 0.141 AC: 1212

ExAC AF: 0.130 AC: 15834

Asia WGS AF: 0.0700 AC: 245 AN: 3478

EpiCase AF: 0.147

EpiControl AF: 0.151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Apr 12, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

PGM1-congenital disorder of glycosylation Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital disorder of glycosylation Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.38	T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	0.044
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.74	N;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.030	N;.;N
REVEL	Benign	0.19
Sift	Benign	1.0	T;.;T
Sift4G	Benign	1.0	T;.;T
Polyphen		0.11	B;.;B
Vest4		0.34
MPC		0.64
ClinPred		0.035	T
GERP RS		5.5
Varity_R		0.14
gMVP		0.55

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: rs855314; hg19: chr1-64095111; COSMIC: COSV64300349;