NM_001360016.2:c.*548C>T

Variant names:

• chrX-154531452-G-A
• rs181015082
• NM_001360016.2:c.*548C>T

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.*548C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 123,832 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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 0.00040 (0 hom., 10 hem., cov: 24)
  • Exomes 𝑓: 0.00060 (0 hom. 2 hem.)
• Consequence: G6PD NM_001360016.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0470
• Publications: 3 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=-0.84).
• BS2: High Hemizygotes in GnomAd4 at 10 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.*548C>T		3_prime_UTR	Exon 13 of 13	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.*548C>T		3_prime_UTR	Exon 13 of 13	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.*548C>T		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.*548C>T		3_prime_UTR	Exon 13 of 13	ENSP00000377192.3	P11413-1
	G6PD	ENST00000915896.1		c.*548C>T		3_prime_UTR	Exon 13 of 13	ENSP00000585955.1
	G6PD	ENST00000439227.6	TSL:5	c.*548C>T		3_prime_UTR	Exon 13 of 13	ENSP00000395599.2	E7EUI8

Frequencies

GnomAD3 genomes AF: 0.000393 AC: 44 AN: 112027 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000945

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000664

GnomAD4 exome AF: 0.000596 AC: 7 AN: 11752 Hom.: 0 Cov.: 0 AF XY: 0.000766 AC XY: 2 AN XY: 2612

African (AFR) AF: 0.00 AC: 0 AN: 217

American (AMR) AF: 0.00 AC: 0 AN: 1966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 146

East Asian (EAS) AF: 0.0172 AC: 7 AN: 408

South Asian (SAS) AF: 0.00 AC: 0 AN: 1123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 577

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 23

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6699

Other (OTH) AF: 0.00 AC: 0 AN: 593

GnomAD4 genome AF: 0.000401 AC: 45 AN: 112080 Hom.: 0 Cov.: 24 AF XY: 0.000292 AC XY: 10 AN XY: 34262

African (AFR) AF: 0.00 AC: 0 AN: 30891

American (AMR) AF: 0.0000944 AC: 1 AN: 10593

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.0118 AC: 42 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2691

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6163

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53104

Other (OTH) AF: 0.00131 AC: 2 AN: 1526

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000638

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	G6PD deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		-0.047
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: rs181015082; hg19: chrX-153759667;