rs137852348

Variant names:

• chrX-154532203-G-A
• rs137852348
• NM_001360016.2:c.1442C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-154532203-G-A
• chrX-154532203-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_001360016.2(G6PD):​c.1442C>T​(p.Pro481Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: G6PD NM_001360016.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.85

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827
• PP5: Variant X-154532203-G-A is Pathogenic according to our data. Variant chrX-154532203-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3771514.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.1442C>T	p.Pro481Leu	missense_variant	Exon 12 of 13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.1532C>T	p.Pro511Leu	missense_variant	Exon 12 of 13		NP_000393.4
G6PD	NM_001042351.3	c.1442C>T	p.Pro481Leu	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.1442C>T	p.Pro481Leu	missense_variant	Exon 12 of 13	1	NM_001360016.2	ENSP00000377192.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097907 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 363335

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000113

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

G6PD: PM1, PM2, PM5 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Pathogenic	0.94	D;D;D;.
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	0.98	.;.;D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.1	L;L;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.5	.;.;D;D
REVEL	Uncertain	0.61
Sift	Benign	0.14	.;.;T;T
Sift4G	Benign	0.61	T;.;T;T
Polyphen		0.0030	B;B;B;.
Vest4		0.64
MutPred		0.56		Loss of disorder (P = 0.0492);Loss of disorder (P = 0.0492);Loss of disorder (P = 0.0492);.;
MVP		0.98
MPC		1.4
ClinPred		0.56	D
GERP RS		4.8
Varity_R		0.36
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs137852348; hg19: chrX-153760418;