rs5030869

Positions:

• chrX-154532990-C-A
• chrX-154532990-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001360016.2(G6PD):​c.1003G>T​(p.Ala335Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: G6PD NM_001360016.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.1003G>T	p.Ala335Ser	missense_variant	9/13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.1093G>T	p.Ala365Ser	missense_variant	9/13		NP_000393.4
G6PD	NM_001042351.3	c.1003G>T	p.Ala335Ser	missense_variant	9/13		NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10	c.1003G>T	p.Ala335Ser	missense_variant	9/13	1	NM_001360016.2	ENSP00000377192	P4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000548 AC: 1 AN: 182482 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67366

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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D;D;D;.;D
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.96	.;.;D;D;T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Benign	1.5	L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.63	.;.;N;N;N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	.;.;D;D;D
Sift4G	Uncertain	0.0030	D;.;D;D;.
Polyphen		0.10	B;B;B;.;.
Vest4		0.43
MutPred		0.66		Gain of glycosylation at A335 (P = 0.0103);Gain of glycosylation at A335 (P = 0.0103);Gain of glycosylation at A335 (P = 0.0103);.;.;
MVP		0.89
MPC		1.7
ClinPred		0.55	D
GERP RS		5.8
Varity_R		0.74
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs5030869; hg19: chrX-153761205;