rs743544

Positions:

• chrX-154536951-G-A
• chrX-154536951-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001360016.2(G6PD):​c.121-773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 112,604 control chromosomes in the GnomAD database, including 192 homozygotes. There are 1,510 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.038 (192 hom., 1510 hem., cov: 24)
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PD	NM_001360016.2	c.121-773C>T		intron_variant		ENST00000393562.10
G6PD	NM_000402.4	c.211-773C>T		intron_variant
G6PD	NM_001042351.3	c.121-773C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10	c.121-773C>T		intron_variant		1	NM_001360016.2	P4

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 4324 AN: 112551 Hom.: 189 Cov.: 24 AF XY: 0.0436 AC XY: 1511 AN XY: 34693

Gnomad AFR AF: 0.00644

Gnomad AMI AF: 0.00729

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0384 AC: 4324 AN: 112604 Hom.: 192 Cov.: 24 AF XY: 0.0434 AC XY: 1510 AN XY: 34756

Gnomad4 AFR AF: 0.00643

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0172 Hom.: 87

Bravo AF: 0.0395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs743544; hg19: chrX-153765166;