rs2230036

Variant names:

• chrX-154532738-C-T
• rs2230036
• NM_001360016.2:c.1116G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001360016.2(G6PD):​c.1116G>A​(p.Gln372Gln) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,210,729 control chromosomes in the GnomAD database, including 260 homozygotes. There are 1,981 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (141 hom., 965 hem., cov: 24)
  • Exomes 𝑓: 0.0034 (119 hom. 1016 hem.)
• Consequence: G6PD NM_001360016.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 7.41
• Publications: 18 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-154532738-C-T is Benign according to our data. Variant chrX-154532738-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 10365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

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.1116G>A	p.Gln372Gln	synonymous	Exon 10 of 13	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.1206G>A	p.Gln402Gln	synonymous	Exon 10 of 13	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.1116G>A	p.Gln372Gln	synonymous	Exon 10 of 13	NP_001035810.1	P11413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000393562.10	TSL:1 MANE Select	c.1116G>A	p.Gln372Gln	synonymous	Exon 10 of 13	ENSP00000377192.3	P11413-1
	G6PD	ENST00000696421.1		c.1116G>A	p.Gln372Gln	synonymous	Exon 10 of 13	ENSP00000512616.1	A0A8Q3SIS5
	G6PD	ENST00000369620.6	TSL:5	c.1254G>A	p.Gln418Gln	synonymous	Exon 10 of 13	ENSP00000358633.2	P11413-2

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 3549 AN: 112977 Hom.: 137 Cov.: 24

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.00888 AC: 1607 AN: 181037 AF XY: 0.00537

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00524

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000298

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00337 AC: 3703 AN: 1097698 Hom.: 119 Cov.: 33 AF XY: 0.00280 AC XY: 1016 AN XY: 363152

African (AFR) AF: 0.110 AC: 2912 AN: 26386

American (AMR) AF: 0.00674 AC: 237 AN: 35166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.000277 AC: 15 AN: 54072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40357

Middle Eastern (MID) AF: 0.00484 AC: 20 AN: 4133

European-Non Finnish (NFE) AF: 0.000133 AC: 112 AN: 841941

Other (OTH) AF: 0.00883 AC: 407 AN: 46079

GnomAD4 genome AF: 0.0315 AC: 3565 AN: 113031 Hom.: 141 Cov.: 24 AF XY: 0.0274 AC XY: 965 AN XY: 35193

African (AFR) AF: 0.107 AC: 3342 AN: 31174

American (AMR) AF: 0.0149 AC: 160 AN: 10768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 2753

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6313

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000356 AC: 19 AN: 53333

Other (OTH) AF: 0.0279 AC: 43 AN: 1540

Alfa AF: 0.0141 Hom.: 548

Bravo AF: 0.0385

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Anemia, nonspherocytic hemolytic, due to G6PD deficiency (2)
-	-	2	G6PD deficiency (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.3
DANN	Benign	0.62
PhyloP100		7.4
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2230036; hg19: chrX-153760953;