Genetic Variant G6PD:c.*50G>A (chrX-154531950-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS2_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.73

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
G6PD	NM_001360016.2 link	c.*50G>A	3_prime_UTR_variant	Exon 13 of 13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4 link	c.*50G>A	3_prime_UTR_variant	Exon 13 of 13		NP_000393.4	P11413-3
G6PD	NM_001042351.3 link	c.*50G>A	3_prime_UTR_variant	Exon 13 of 13		NP_001035810.1	P11413-1A0A384NL00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562 link	c.*50G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_001360016.2	ENSP00000377192.3		P11413-1

Frequencies

GnomAD3 genomes

AF:

0.000331

AC:

AN:

87486

Hom.:

Cov.:

show subpopulations

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:

AN:

135932

AF XY:

0.000121

show subpopulations

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:

AN:

825403

Hom.:

Cov.:

AF XY:

0.0000711

AC XY:

AN XY:

253167

show subpopulations

Gnomad4 AFR exome

AF:

0.000856

AC:

AN:

19863

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

26987

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

12249

Gnomad4 EAS exome

AF:

0.0000738

AC:

AN:

13542

Gnomad4 SAS exome

AF:

0.000231

AC:

AN:

47559

Gnomad4 FIN exome

AF:

0.0000420

AC:

AN:

23803

Gnomad4 NFE exome

AF:

0.00000463

AC:

AN:

647311

Gnomad4 Remaining exome

AF:

0.0000958

AC:

AN:

31300

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000331

AC:

AN:

87515

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

22185

show subpopulations

Gnomad4 AFR

AF:

0.00110

AC:

0.00109983

AN:

0.00109983

Gnomad4 AMR

AF:

0.000133

AC:

0.000132873

AN:

0.000132873

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000447

AC:

0.0000446578

AN:

0.0000446578

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000234

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 14, 2012

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.018

DANN

Benign

0.58

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over