chrX-154536951-G-A

Variant names:

• chrX-154536951-G-A
• rs743544
• NM_001360016.2:c.121-773C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

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.121-773C>T		intron	N/A	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.211-773C>T		intron	N/A	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.121-773C>T		intron	N/A	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.121-773C>T		intron	N/A	ENSP00000377192.3	P11413-1
	G6PD	ENST00000696421.1		c.121-773C>T		intron	N/A	ENSP00000512616.1	A0A8Q3SIS5
	G6PD	ENST00000369620.6	TSL:5	c.121-773C>T		intron	N/A	ENSP00000358633.2	P11413-2

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 4324 AN: 112551 Hom.: 189 Cov.: 24

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

African (AFR) AF: 0.00643 AC: 200 AN: 31119

American (AMR) AF: 0.0557 AC: 593 AN: 10651

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 80 AN: 2646

East Asian (EAS) AF: 0.331 AC: 1182 AN: 3567

South Asian (SAS) AF: 0.0470 AC: 130 AN: 2767

European-Finnish (FIN) AF: 0.0715 AC: 438 AN: 6128

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 218

European-Non Finnish (NFE) AF: 0.0307 AC: 1633 AN: 53276

Other (OTH) AF: 0.0388 AC: 60 AN: 1546

Alfa AF: 0.0172 Hom.: 87

Bravo AF: 0.0395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs743544; hg19: chrX-153765166;