NM_021971.4:c.551A>G

Variant names:

Variant summary

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

The NM_021971.4(GMPPB):c.551A>G(p.Gln184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,614,016 control chromosomes in the GnomAD database, including 803,498 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74544 hom., cov: 34)

Exomes 𝑓: 1.0 ( 728954 hom. )

Consequence

GMPPB
NM_021971.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.893

Publications

37 publications found

Variant links:

Genes affected

GMPPB (HGNC:22932): (GDP-mannose pyrophosphorylase B) This gene is thought to encode a GDP-mannose pyrophosphorylase. The encoded protein catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, a reaction involved in the production of N-linked oligosaccharides. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2009]

GMPPB Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
myopathy caused by variation in GMPPB
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2T
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
congenital myasthenic syndrome
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital myasthenic syndromes with glycosylation defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GMPPB 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=8.3081846E-7).

BP6

Variant 3-49722606-T-C is Benign according to our data. Variant chr3-49722606-T-C is described in ClinVar as Benign. ClinVar VariationId is 1169340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPPB	NM_021971.4	MANE Select	c.551A>G	p.Gln184Arg	missense	Exon 5 of 9	NP_068806.2
	GMPPB	NM_013334.4		c.551A>G	p.Gln184Arg	missense	Exon 5 of 8	NP_037466.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GMPPB	ENST00000308388.7	TSL:1 MANE Select	c.551A>G	p.Gln184Arg	missense	Exon 5 of 9	ENSP00000311130.6
GMPPB	ENST00000495627.2	TSL:2	c.659A>G	p.Gln220Arg	missense	Exon 5 of 9	ENSP00000503768.1
GMPPB	ENST00000308375.10	TSL:2	c.551A>G	p.Gln184Arg	missense	Exon 5 of 8	ENSP00000309092.6

Frequencies

GnomAD3 genomes

AF:

0.989

AC:

150579

AN:

152220

Hom.:

74494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.964

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.994

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.990

GnomAD2 exomes

AF:

0.997

AC:

250206

AN:

250922

AF XY:

0.998

show subpopulations

Gnomad AFR exome

AF:

0.963

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.999

AC:

1459765

AN:

1461678

Hom.:

728954

Cov.:

AF XY:

0.999

AC XY:

726251

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.961

AC:

32175

AN:

33480

American (AMR)

AF:

0.997

AC:

44578

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26116

AN:

26116

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39698

South Asian (SAS)

AF:

1.00

AC:

86217

AN:

86248

European-Finnish (FIN)

AF:

1.00

AC:

53356

AN:

53356

Middle Eastern (MID)

AF:

0.996

AC:

5746

AN:

5768

European-Non Finnish (NFE)

AF:

1.00

AC:

1111711

AN:

1111906

Other (OTH)

AF:

0.996

AC:

60168

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

114

228

342

456

570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21672

43344

65016

86688

108360

<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:

0.989

AC:

150688

AN:

152338

Hom.:

74544

Cov.:

AF XY:

0.989

AC XY:

73675

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.964

AC:

40050

AN:

41556

American (AMR)

AF:

0.994

AC:

15215

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5188

AN:

5188

South Asian (SAS)

AF:

0.999

AC:

4822

AN:

4826

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68018

AN:

68044

Other (OTH)

AF:

0.991

AC:

2096

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

157

236

314

393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.996

Hom.:

134483

Bravo

AF:

0.987

TwinsUK

AF:

0.999

AC:

3706

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.968

AC:

4267

ESP6500EA

AF:

1.00

AC:

8598

ExAC

AF:

0.997

AC:

121008

Asia WGS

AF:

0.997

AC:

3467

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14;C3809221:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14;C4518000:Autosomal recessive limb-girdle muscular dystrophy type 2T

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Autosomal recessive limb-girdle muscular dystrophy type 2T

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.011

(source)

DANN

Benign

0.82

DEOGEN2

Uncertain

0.48

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.62

MetaRNN

Benign

8.3e-7

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.49

PhyloP100

-0.89

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

REVEL

Benign

0.29

Sift

Benign

0.071

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.019

MPC

0.59

ClinPred

0.0060

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.25

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over