ENST00000696421.1:c.1565G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000696421.1(G6PD):​c.1565G>C​(p.Arg522Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000908 in 110,106 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R522Q) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 22)
• Consequence: G6PD ENST00000696421.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000696421.1	c.1565G>C	p.Arg522Pro	missense_variant	Exon 13 of 13			ENSP00000512616.1
G6PD	ENST00000696420.1	c.1458-45G>C		intron_variant	Intron 12 of 12			ENSP00000512615.1
G6PD	ENST00000567614.1	n.291G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00000909 AC: 1 AN: 110053 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32309

Gnomad AFR AF: 0.0000331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000908 AC: 1 AN: 110106 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32372

Gnomad4 AFR AF: 0.0000331

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.5
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;