X-154521905-T-C

Variant names:

• chrX-154521905-T-C
• rs622
• ENST00000696421.1:c.1458-3457A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000696421.1(G6PD):​c.1458-3457A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.52 (11682 hom., 15807 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: G6PD ENST00000696421.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 14 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

LOC124905229 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696421.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000696421.1		c.1458-3457A>G		intron	N/A	ENSP00000512616.1
	G6PD	ENST00000696420.1		c.1458-3609A>G		intron	N/A	ENSP00000512615.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 56667 AN: 107935 Hom.: 11687 Cov.: 21

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.545

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.525 AC: 56668 AN: 107985 Hom.: 11682 Cov.: 21 AF XY: 0.513 AC XY: 15807 AN XY: 30811

African (AFR) AF: 0.309 AC: 9273 AN: 29983

American (AMR) AF: 0.533 AC: 5368 AN: 10072

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 1509 AN: 2598

East Asian (EAS) AF: 0.798 AC: 2727 AN: 3418

South Asian (SAS) AF: 0.439 AC: 1079 AN: 2457

European-Finnish (FIN) AF: 0.638 AC: 3506 AN: 5499

Middle Eastern (MID) AF: 0.617 AC: 127 AN: 206

European-Non Finnish (NFE) AF: 0.617 AC: 31857 AN: 51637

Other (OTH) AF: 0.540 AC: 795 AN: 1472

Alfa AF: 0.550 Hom.: 3927

Bravo AF: 0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
PhyloP100		0.055

Splicing

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

Other links and lift over

dbSNP: rs622; hg19: chrX-153750119;