chrX-154518341-C-T

Variant names:

• chrX-154518341-C-T
• rs190740563
• ENST00000696421.1:c.1565G>A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BS2_Supporting

The ENST00000696421.1(G6PD):​c.1565G>A​(p.Arg522Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 110,106 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., 23 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: G6PD ENST00000696421.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.870

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]

LOC124905229 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-154518341-C-T is Benign according to our data. Variant chrX-154518341-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3771853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 23 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124905229	XR_007068357.1	n.236+2626C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000696421.1	c.1565G>A	p.Arg522Gln	missense_variant	Exon 13 of 13			ENSP00000512616.1
G6PD	ENST00000696420.1	c.1458-45G>A		intron_variant	Intron 12 of 12			ENSP00000512615.1
G6PD	ENST00000567614.1	n.291G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 134 AN: 110053 Hom.: 0 Cov.: 22 AF XY: 0.000712 AC XY: 23 AN XY: 32309

Gnomad AFR AF: 0.000232

Gnomad AMI AF: 0.00443

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00266

Gnomad EAS AF: 0.000285

Gnomad SAS AF: 0.00115

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.00135

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00122 AC: 134 AN: 110106 Hom.: 0 Cov.: 22 AF XY: 0.000710 AC XY: 23 AN XY: 32372

Gnomad4 AFR AF: 0.000231

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00266

Gnomad4 EAS AF: 0.000286

Gnomad4 SAS AF: 0.00116

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00195

Gnomad4 OTH AF: 0.00134

Alfa AF: 0.00103 Hom.: 7

Bravo AF: 0.00120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

G6PD: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs190740563; hg19: chrX-153746665;