X-154532439-A-G

Variant names:

• chrX-154532439-A-G
• rs2230037
• NM_001360016.2:c.1311T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP6_Moderate BP7

The NM_001360016.2(G6PD):​c.1311T>C​(p.Tyr437Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position has been classified as Uncertain significance.

• 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
• Publications: 116 publications found

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 Gene-Disease associations (from GenCC):

• anemia, nonspherocytic hemolytic, due to G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• class I glucose-6-phosphate dehydrogenase deficiency

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 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 VariationId is 470162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	NM_001360016.2	MANE Select	c.1311T>C	p.Tyr437Tyr	synonymous	Exon 11 of 13	NP_001346945.1
	G6PD	NM_000402.4		c.1401T>C	p.Tyr467Tyr	synonymous	Exon 11 of 13	NP_000393.4
	G6PD	NM_001042351.3		c.1311T>C	p.Tyr437Tyr	synonymous	Exon 11 of 13	NP_001035810.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000393562.10	TSL:1 MANE Select	c.1311T>C	p.Tyr437Tyr	synonymous	Exon 11 of 13	ENSP00000377192.3
	G6PD	ENST00000696421.1		c.1311T>C	p.Tyr437Tyr	synonymous	Exon 11 of 13	ENSP00000512616.1
	G6PD	ENST00000369620.6	TSL:5	c.1449T>C	p.Tyr483Tyr	synonymous	Exon 11 of 13	ENSP00000358633.2

Frequencies

GnomAD3 genomes AF: 0.832 AC: 92541 AN: 111243 Hom.: 27365 Cov.: 24

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

African (AFR) AF: 0.743 AC: 19620 AN: 26399

American (AMR) AF: 0.806 AC: 28348 AN: 35155

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 15524 AN: 19386

East Asian (EAS) AF: 0.933 AC: 28167 AN: 30203

South Asian (SAS) AF: 0.617 AC: 33423 AN: 54141

European-Finnish (FIN) AF: 0.920 AC: 37025 AN: 40259

Middle Eastern (MID) AF: 0.741 AC: 3062 AN: 4134

European-Non Finnish (NFE) AF: 0.888 AC: 747648 AN: 841949

Other (OTH) AF: 0.841 AC: 38760 AN: 46087

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

African (AFR) AF: 0.745 AC: 22814 AN: 30620

American (AMR) AF: 0.821 AC: 8682 AN: 10572

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2117 AN: 2640

East Asian (EAS) AF: 0.883 AC: 3057 AN: 3461

South Asian (SAS) AF: 0.578 AC: 1570 AN: 2718

European-Finnish (FIN) AF: 0.927 AC: 5543 AN: 5981

Middle Eastern (MID) AF: 0.829 AC: 180 AN: 217

European-Non Finnish (NFE) AF: 0.884 AC: 46773 AN: 52906

Other (OTH) AF: 0.833 AC: 1254 AN: 1506

Alfa AF: 0.856 Hom.: 84509

Bravo AF: 0.829

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Anemia, nonspherocytic hemolytic, due to G6PD deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	0.0040
PhyloP100		-2.6
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

Other links and lift over

dbSNP: rs2230037; hg19: chrX-153760654;