rs267606836

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001360016.2(G6PD):c.544C>T(p.Arg182Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,209,651 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

G6PD
NM_001360016.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

G6PD (HGNC:4057): (glucose-6-phosphate dehydrogenase) This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

G6PD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PD	NM_001360016.2 link	c.544C>T	p.Arg182Trp	missense_variant	Exon 6 of 13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4 link	c.634C>T	p.Arg212Trp	missense_variant	Exon 6 of 13		NP_000393.4	P11413-3
G6PD	NM_001042351.3 link	c.544C>T	p.Arg182Trp	missense_variant	Exon 6 of 13		NP_001035810.1	P11413-1A0A384NL00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10 link	c.544C>T	p.Arg182Trp	missense_variant	Exon 6 of 13	1	NM_001360016.2	ENSP00000377192.3		P11413-1

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111792

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34012

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183118

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000455

AC:

AN:

1097859

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363261

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111792

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34012

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 13, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: G6PD c.634C>T (p.Arg212Trp) results in a non-conservative amino acid change located in the Glucose-6-phosphate dehydrogenase, C-terminal of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 183118 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.634C>T also known as c.544C>T, p.R182W has been reported as part of a haplotype c.[317C>G;544C>T;592C>T] in the literature in individuals affected with Glucose 6 Phosphate Dehydrogenase Deficiency (example: Maeda_1992) . These report(s) do not provide unequivocal conclusions about association of the variant with Glucose 6 Phosphate Dehydrogenase Deficiency. To our knowledge, experimental evidence demonstrating an impact on protein function for this variant alone has not been reported. The following publication has been ascertained in the context of this evaluation (PMID: 1353664). ClinVar contains an entry for this variant (Variation ID: 242750). Based on the evidence outlined above, this variant alone was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.93

D;D;D;.;D;.;D

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.95

.;.;D;D;D;D;D

M_CAP

Uncertain

0.094

MetaRNN

Uncertain

0.52

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Benign

1.9

L;L;L;L;.;.;.

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.6

.;.;D;D;D;D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

.;.;D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;.;D;D;.;.;.

Polyphen

0.44

B;B;B;.;.;.;.

Vest4

0.58

MVP

0.96

MPC

0.30

ClinPred

0.35

GERP RS

2.6

Varity_R

0.49

gMVP

0.75

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