Variant X-154534345-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001360016.2(G6PD):c.637G>C(p.Val213Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,948 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

G6PD
NM_001360016.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.93

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PD	NM_001360016.2 linkuse as main transcript	c.637G>C	p.Val213Leu	missense_variant	6/13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4 linkuse as main transcript	c.727G>C	p.Val243Leu	missense_variant	6/13		NP_000393.4	P11413-3
G6PD	NM_001042351.3 linkuse as main transcript	c.637G>C	p.Val213Leu	missense_variant	6/13		NP_001035810.1	P11413-1A0A384NL00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10 linkuse as main transcript	c.637G>C	p.Val213Leu	missense_variant	6/13	1	NM_001360016.2	ENSP00000377192.3		P11413-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183004

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000182

AC:

AN:

1097948

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.59

BayesDel_noAF

Pathogenic

0.61

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.90

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

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

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

M_CAP

Pathogenic

0.31

MetaRNN

Pathogenic

0.92

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

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.8

M;M;M;M;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.8

.;.;N;N;N;N;N

REVEL

Pathogenic

0.69

Sift

Uncertain

0.024

.;.;D;T;D;D;D

Sift4G

Benign

0.072

T;.;T;D;.;.;.

Polyphen

0.0060

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

Vest4

0.71

MutPred

0.87

Loss of MoRF binding (P = 0.1222);Loss of MoRF binding (P = 0.1222);Loss of MoRF binding (P = 0.1222);Loss of MoRF binding (P = 0.1222);.;.;Loss of MoRF binding (P = 0.1222);

MVP

1.0

MPC

1.2

ClinPred

0.60

GERP RS

4.6

Varity_R

0.85

gMVP

0.99

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over