rs6676290

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.30

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]

PGM1 links:

PGM1 (HGNC:):

PGM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PGM1	NM_002633.3 linkuse as main transcript	c.1501G>A	p.Val501Ile	missense_variant	10/11	ENST00000371084.8	NP_002624.2	P36871-1
PGM1	NM_001172818.1 linkuse as main transcript	c.1555G>A	p.Val519Ile	missense_variant	10/11		NP_001166289.1	P36871-2B7Z6C2
PGM1	NM_001172819.2 linkuse as main transcript	c.910G>A	p.Val304Ile	missense_variant	10/11		NP_001166290.1	P36871-3B4DDQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8 linkuse as main transcript	c.1501G>A	p.Val501Ile	missense_variant	10/11	1	NM_002633.3	ENSP00000360125.3		P36871-1

Frequencies

GnomAD3 genomes

AF:

0.0461

AC:

7015

AN:

152112

Hom.:

558

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00427

AC XY:

3103

AN XY:

727128

show subpopulations

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.:

AF XY:

0.0449

AC XY:

3341

AN XY:

74442

show subpopulations

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:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.147

AC:

647

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0152

AC:

1840

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 14, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PGM1-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.36

T;.;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.69

T;T;T;T

MetaRNN

Benign

0.0012

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

N;.;.;.

PrimateAI

Uncertain

0.66

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

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over