chrX-154531950-C-T

Variant names:

• chrX-154531950-C-T
• rs201294737
• NM_001360016.2:c.*50G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001360016.2(G6PD):​c.*50G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 912,918 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., 3 hem., cov: 20)
  • Exomes 𝑓: 0.000044 (0 hom. 18 hem.)
• Consequence: G6PD NM_001360016.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.73
• Publications: 0 publications found

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]

G6PD Gene-Disease associations (from GenCC):

• anemia, nonspherocytic hemolytic, due to G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• class I glucose-6-phosphate dehydrogenase deficiency

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Hemizygotes in GnomAd4 at 3 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	NM_001360016.2	MANE Select	c.*50G>A		3_prime_UTR	Exon 13 of 13	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.*50G>A		3_prime_UTR	Exon 13 of 13	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.*50G>A		3_prime_UTR	Exon 13 of 13	NP_001035810.1	P11413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000393562.10	TSL:1 MANE Select	c.*50G>A		3_prime_UTR	Exon 13 of 13	ENSP00000377192.3	P11413-1
	G6PD	ENST00000915896.1		c.*50G>A		3_prime_UTR	Exon 13 of 13	ENSP00000585955.1
	G6PD	ENST00000439227.6	TSL:5	c.*50G>A		3_prime_UTR	Exon 13 of 13	ENSP00000395599.2	E7EUI8

Frequencies

GnomAD3 genomes AF: 0.000331 AC: 29 AN: 87486 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

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: 0.0000447

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000110 AC: 15 AN: 135932 AF XY: 0.000121

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000890

Gnomad FIN exome AF: 0.0000792

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000279

GnomAD4 exome AF: 0.0000436 AC: 36 AN: 825403 Hom.: 0 Cov.: 32 AF XY: 0.0000711 AC XY: 18 AN XY: 253167

African (AFR) AF: 0.000856 AC: 17 AN: 19863

American (AMR) AF: 0.00 AC: 0 AN: 26987

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12249

East Asian (EAS) AF: 0.0000738 AC: 1 AN: 13542

South Asian (SAS) AF: 0.000231 AC: 11 AN: 47559

European-Finnish (FIN) AF: 0.0000420 AC: 1 AN: 23803

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2789

European-Non Finnish (NFE) AF: 0.00000463 AC: 3 AN: 647311

Other (OTH) AF: 0.0000958 AC: 3 AN: 31300

GnomAD4 genome AF: 0.000331 AC: 29 AN: 87515 Hom.: 0 Cov.: 20 AF XY: 0.000135 AC XY: 3 AN XY: 22185

African (AFR) AF: 0.00110 AC: 26 AN: 23640

American (AMR) AF: 0.000133 AC: 1 AN: 7526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2239

East Asian (EAS) AF: 0.00 AC: 0 AN: 2417

South Asian (SAS) AF: 0.00 AC: 0 AN: 1523

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3435

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 199

European-Non Finnish (NFE) AF: 0.0000447 AC: 2 AN: 44785

Other (OTH) AF: 0.00 AC: 0 AN: 1152

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000234

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.018
DANN	Benign	0.58
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201294737; hg19: chrX-153760165;