Genetic Variant GMDS:p.Gly17Ser (chr6-2245374-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001500.4(GMDS):c.49G>A(p.Gly17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000974 in 1,550,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

GMDS
NM_001500.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.831

Publications

0 publications found

Variant links:

Genes affected

GMDS (HGNC:4369): (GDP-mannose 4,6-dehydratase) GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans (MIM 137020).[supplied by OMIM, Aug 2009]

GMDS links:

GMDS-DT (HGNC:48993): (GMDS divergent transcript)

GMDS-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005196035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001500.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMDS	NM_001500.4	MANE Select	c.49G>A	p.Gly17Ser	missense	Exon 1 of 11	NP_001491.1	O60547-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GMDS	ENST00000380815.5	TSL:1 MANE Select	c.49G>A	p.Gly17Ser	missense	Exon 1 of 11	ENSP00000370194.4	O60547-1
GMDS	ENST00000950953.1		c.49G>A	p.Gly17Ser	missense	Exon 1 of 12	ENSP00000621012.1
GMDS	ENST00000851213.1		c.49G>A	p.Gly17Ser	missense	Exon 1 of 12	ENSP00000521272.1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000726

AC:

AN:

151438

AF XY:

0.0000599

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.0000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000529

AC:

AN:

1398436

Hom.:

Cov.:

AF XY:

0.0000433

AC XY:

AN XY:

692076

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

31122

American (AMR)

AF:

0.0000529

AC:

AN:

37798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24938

East Asian (EAS)

AF:

0.00

AC:

AN:

36310

South Asian (SAS)

AF:

0.00

AC:

AN:

80432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4406

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1085876

Other (OTH)

AF:

0.000120

AC:

AN:

58158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000506

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000215

Hom.:

Bravo

AF:

0.000657

ESP6500AA

AF:

0.00118

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000152

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.83

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.63

REVEL

Benign

0.047

Sift

Benign

0.14

Sift4G

Benign

0.13

Polyphen

0.0040

Vest4

0.12

MVP

0.37

MPC

0.79

ClinPred

0.052

GERP RS

3.7

PromoterAI

-0.0049

Neutral

(source)

Varity_R

0.10

gMVP

0.55

Mutation Taster

=82/18

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over