chr6-83170448-C-T

Position:

chr6-83170448-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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 links:

DOP1A (HGNC:):

DOP1A 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=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 id 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/exons	MANE	Protein	UniProt
PGM3	NM_015599.3 linkuse as main transcript	c.1396G>A	p.Asp466Asn	missense_variant	12/13	ENST00000513973.6	NP_056414.1	O95394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM3	ENST00000513973.6 linkuse as main transcript	c.1396G>A	p.Asp466Asn	missense_variant	12/13	1	NM_015599.3	ENSP00000424874.1		O95394-1
PGM3	ENST00000283977.9 linkuse as main transcript	c.1153G>A	p.Asp385Asn	missense_variant	11/12	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

GnomAD3 exomes

AF:

0.274

AC:

68811

AN:

251322

Hom.:

10235

AF XY:

0.266

AC XY:

36192

AN XY:

135820

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 SAS exome

AF:

0.233

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

Gnomad4 AFR exome

AF:

0.569

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.344

AC:

52221

AN:

151988

Hom.:

10368

Cov.:

AF XY:

0.341

AC XY:

25365

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.316

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.268

Hom.:

14702

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

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;.;.;.

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

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

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