X-154532439-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The NM_001360016.2(G6PD):c.1311T>C(p.Tyr437=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (27364 hom., 27660 hem., cov: 24)
  • Exomes 𝑓: 0.87 (280377 hom. 311397 hem.)
  • Failed GnomAD Quality Control
• Consequence: G6PD NM_001360016.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.64

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 -7 ACMG points.

• BP6: Variant X-154532439-A-G is Benign according to our data. Variant chrX-154532439-A-G is described in ClinVar as [Benign]. Clinvar id is 470162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 27365 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PD	NM_001360016.2	c.1311T>C	p.Tyr437=	synonymous_variant	11/13	ENST00000393562.10
G6PD	NM_000402.4	c.1401T>C	p.Tyr467=	synonymous_variant	11/13
G6PD	NM_001042351.3	c.1311T>C	p.Tyr437=	synonymous_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10	c.1311T>C	p.Tyr437=	synonymous_variant	11/13	1	NM_001360016.2	P4

Frequencies

GnomAD3 genomes AF: 0.832 AC: 92541 AN: 111243 Hom.: 27365 Cov.: 24 AF XY: 0.826 AC XY: 27610 AN XY: 33441

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.830

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.867 AC: 951577 AN: 1097713 Hom.: 280377 Cov.: 58 AF XY: 0.857 AC XY: 311397 AN XY: 363219

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.806

Gnomad4 ASJ exome AF: 0.801

Gnomad4 EAS exome AF: 0.933

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.920

Gnomad4 NFE exome AF: 0.888

Gnomad4 OTH exome AF: 0.841

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.832 AC: 92585 AN: 111295 Hom.: 27364 Cov.: 24 AF XY: 0.826 AC XY: 27660 AN XY: 33503

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.833

Alfa AF: 0.869 Hom.: 66387

Bravo AF: 0.829

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	0.0040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2230037; hg19: chrX-153760654;