rs473267

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015599.3(PGM3):c.1396G>A(p.Asp466Asn) variant causes a missense change. The variant allele was found at a frequency of 0.273 in 1,612,928 control chromosomes in the GnomAD database, including 64,262 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. D466D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.34 ( 10368 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53894 hom. )

Consequence

PGM3
NM_015599.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.61

Publications

45 publications found

Variant links:

Genes affected

PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

PGM3 links:

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

DOP1A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DOP1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.9459846E-5).

BP6

Variant 6-83170448-C-T is Benign according to our data. Variant chr6-83170448-C-T is described in ClinVar as Benign. ClinVar VariationId is 681218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM3	NM_015599.3 link	c.1396G>A	p.Asp466Asn	missense_variant	Exon 12 of 13	ENST00000513973.6	NP_056414.1	O95394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM3	ENST00000513973.6 link	c.1396G>A	p.Asp466Asn	missense_variant	Exon 12 of 13	1	NM_015599.3	ENSP00000424874.1		O95394-1
PGM3	ENST00000283977.9 link	c.1153G>A	p.Asp385Asn	missense_variant	Exon 11 of 12	5		ENSP00000283977.5		J3KN95

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52127

AN:

151870

Hom.:

10327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.315

GnomAD2 exomes

AF:

0.274

AC:

68811

AN:

251322

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.266

AC:

388225

AN:

1460940

Hom.:

53894

Cov.:

AF XY:

0.263

AC XY:

191331

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.569

AC:

19044

AN:

33448

American (AMR)

AF:

0.258

AC:

11551

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5092

AN:

26128

East Asian (EAS)

AF:

0.306

AC:

12154

AN:

39684

South Asian (SAS)

AF:

0.235

AC:

20298

AN:

86238

European-Finnish (FIN)

AF:

0.265

AC:

14136

AN:

53418

Middle Eastern (MID)

AF:

0.216

AC:

1243

AN:

5766

European-Non Finnish (NFE)

AF:

0.259

AC:

288018

AN:

1111176

Other (OTH)

AF:

0.276

AC:

16689

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

13418

26837

40255

53674

67092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9852

19704

29556

39408

49260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.344

AC:

52221

AN:

151988

Hom.:

10368

Cov.:

AF XY:

0.341

AC XY:

25365

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.553

AC:

22911

AN:

41406

American (AMR)

AF:

0.307

AC:

4688

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

682

AN:

3468

East Asian (EAS)

AF:

0.316

AC:

1634

AN:

5174

South Asian (SAS)

AF:

0.231

AC:

1112

AN:

4824

European-Finnish (FIN)

AF:

0.266

AC:

2809

AN:

10572

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17503

AN:

67952

Other (OTH)

AF:

0.316

AC:

667

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1626

3253

4879

6506

8132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.282

Hom.:

22811

Bravo

AF:

0.353

TwinsUK

AF:

0.253

AC:

939

ALSPAC

AF:

0.258

AC:

993

ESP6500AA

AF:

0.548

AC:

2414

ESP6500EA

AF:

0.253

AC:

2174

ExAC

AF:

0.278

AC:

33764

Asia WGS

AF:

0.284

AC:

988

AN:

3478

EpiCase

AF:

0.245

EpiControl

AF:

0.245

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

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. -

Immunodeficiency 23

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;T;.;.;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

T;T;T;T;T;.

MetaRNN

Benign

0.000059

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;L;.;.;.

PhyloP100

3.6

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.5

N;.;N;D;N;D

REVEL

Benign

0.15

Sift

Benign

0.17

T;.;T;T;T;T

Sift4G

Benign

0.31

T;T;T;T;T;T

Polyphen

0.24

B;.;.;.;.;.

Vest4

0.15

MPC

0.33

ClinPred

0.031

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.70

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over