rs72554664

Variant names:

• chrX-154532257-C-A
• NM_001360016.2:c.1388G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-154532257-C-A
• chrX-154532257-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_Moderate

The NM_001360016.2(G6PD):​c.1388G>T​(p.Arg463Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: G6PD NM_001360016.2 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.34

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948
• PP5: Variant X-154532257-C-A is Pathogenic according to our data. Variant chrX-154532257-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 2504081.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.1388G>T	p.Arg463Leu	missense_variant	Exon 12 of 13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.1478G>T	p.Arg493Leu	missense_variant	Exon 12 of 13		NP_000393.4
G6PD	NM_001042351.3	c.1388G>T	p.Arg463Leu	missense_variant	Exon 12 of 13		NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10	c.1388G>T	p.Arg463Leu	missense_variant	Exon 12 of 13	1	NM_001360016.2	ENSP00000377192.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency Pathogenic:1

Sep 30, 2022

Pediatrics, Sichuan Provincial Hospital For Women And Children

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: provider interpretation

At admission, the boy's height was 78cm, weight was 8kg, head circumference was 41cm, HGB was 37g/L, reticulocyte ratio was 12.19%, a level of G6PD enzyme activity was 1121U/L. According to ACMG guidelines, this variant was determined to be PS3+PS4+PM1+PM5 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.72	D
BayesDel_noAF	Pathogenic	0.79
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.98	D;D;D;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	1.0	.;.;D;D
M_CAP	Pathogenic	0.96	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	3.7	H;H;H;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.2	.;.;D;D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0020	.;.;D;D
Sift4G	Uncertain	0.010	D;.;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.91
MutPred		0.73		Loss of phosphorylation at T466 (P = 0.124);Loss of phosphorylation at T466 (P = 0.124);Loss of phosphorylation at T466 (P = 0.124);.;
MVP		1.0
MPC		2.3
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.97
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153760472;