X-154532945-C-T

Variant names:

• chrX-154532945-C-T
• rs34193178
• NM_001360016.2:c.1048G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001360016.2(G6PD):​c.1048G>A​(p.Asp350Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,182 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: G6PD NM_001360016.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.1048G>A	p.Asp350Asn	missense_variant	Exon 9 of 13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.1138G>A	p.Asp380Asn	missense_variant	Exon 9 of 13		NP_000393.4
G6PD	NM_001042351.3	c.1048G>A	p.Asp350Asn	missense_variant	Exon 9 of 13		NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10	c.1048G>A	p.Asp350Asn	missense_variant	Exon 9 of 13	1	NM_001360016.2	ENSP00000377192.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000547 AC: 1 AN: 182804 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67436

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000524

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098182 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 363554

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: 0.00

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	D;D;D;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	.;.;D;D
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	.;.;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	.;.;D;D
Sift4G	Uncertain	0.0080	D;.;D;D
Polyphen		0.44	B;B;B;.
Vest4		0.53
MutPred		0.58		Gain of MoRF binding (P = 0.0858);Gain of MoRF binding (P = 0.0858);Gain of MoRF binding (P = 0.0858);.;
MVP		0.98
MPC		1.8
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.77
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs34193178; hg19: chrX-153761160;