6-83191204-A-T

Variant names:

Variant summary

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

The NM_001199917.2(PGM3):c.65T>A(p.Val22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 1,534,568 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V22A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.030 ( 164 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 330 hom. )

Consequence

PGM3
NM_001199917.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0380

Publications

6 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 Gene-Disease associations (from GenCC):

immunodeficiency 23
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

PGM3 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=0.0019480586).

BP6

Variant 6-83191204-A-T is Benign according to our data. Variant chr6-83191204-A-T is described in ClinVar as Benign. ClinVar VariationId is 475004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGM3	NM_015599.3	MANE Select	c.-2-190T>A		intron	N/A	NP_056414.1	O95394-1
PGM3	NM_001199917.2		c.65T>A	p.Val22Asp	missense	Exon 2 of 14	NP_001186846.1	O95394-4
PGM3	NM_001367287.1		c.65T>A	p.Val22Asp	missense	Exon 2 of 14	NP_001354216.1	O95394-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGM3	ENST00000513973.6	TSL:1 MANE Select	c.-2-190T>A	intron	N/A	ENSP00000424874.1	O95394-1
PGM3	ENST00000512866.5	TSL:1	c.-2-190T>A	intron	N/A	ENSP00000421565.1	O95394-3
PGM3	ENST00000283977.9	TSL:5	c.-40+1975T>A	intron	N/A	ENSP00000283977.5	J3KN95

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4490

AN:

151994

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0271

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0838

Gnomad SAS

AF:

0.0358

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0202

AC:

2637

AN:

130380

AF XY:

0.0204

show subpopulations

Gnomad AFR exome

AF:

0.0900

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0830

Gnomad FIN exome

AF:

0.000368

Gnomad NFE exome

AF:

0.000983

Gnomad OTH exome

AF:

0.00870

GnomAD4 exome

AF:

0.00725

AC:

10023

AN:

1382456

Hom.:

330

Cov.:

AF XY:

0.00785

AC XY:

5357

AN XY:

682220

show subpopulations

African (AFR)

AF:

0.0870

AC:

2745

AN:

31546

American (AMR)

AF:

0.0153

AC:

548

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25178

East Asian (EAS)

AF:

0.0686

AC:

2449

AN:

35714

South Asian (SAS)

AF:

0.0330

AC:

2614

AN:

79206

European-Finnish (FIN)

AF:

0.000418

AC:

AN:

33522

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000709

AC:

764

AN:

1078038

Other (OTH)

AF:

0.0143

AC:

825

AN:

57854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

493

986

1480

1973

2466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.0296

AC:

4502

AN:

152112

Hom.:

164

Cov.:

AF XY:

0.0300

AC XY:

2228

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0811

AC:

3363

AN:

41458

American (AMR)

AF:

0.0270

AC:

413

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0839

AC:

432

AN:

5152

South Asian (SAS)

AF:

0.0359

AC:

173

AN:

4822

European-Finnish (FIN)

AF:

0.000566

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

68008

Other (OTH)

AF:

0.0265

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

211

422

632

843

1054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.00481

Hom.:

Bravo

AF:

0.0327

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0107

AC:

461

Asia WGS

AF:

0.0620

AC:

214

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 23 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.5

(source)

DANN

Benign

0.56

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.99

PhyloP100

-0.038

PrimateAI

Benign

0.35

PROVEAN

Benign

0.34

REVEL

Benign

0.076

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Vest4

0.069

MPC

0.32

ClinPred

0.0050

GERP RS

-0.79

gMVP

0.84

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over