dbSNP rs201294737: 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

Publications

0 publications found

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 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

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.

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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:

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

African (AFR)

AF:

0.000856

AC:

AN:

19863

American (AMR)

AF:

0.00

AC:

AN:

26987

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12249

East Asian (EAS)

AF:

0.0000738

AC:

AN:

13542

South Asian (SAS)

AF:

0.000231

AC:

AN:

47559

European-Finnish (FIN)

AF:

0.0000420

AC:

AN:

23803

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2789

European-Non Finnish (NFE)

AF:

0.00000463

AC:

AN:

647311

Other (OTH)

AF:

0.0000958

AC:

AN:

31300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.00110

AC:

AN:

23640

American (AMR)

AF:

0.000133

AC:

AN:

7526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2239

East Asian (EAS)

AF:

0.00

AC:

AN:

2417

South Asian (SAS)

AF:

0.00

AC:

AN:

1523

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3435

Middle Eastern (MID)

AF:

0.00

AC:

AN:

199

European-Non Finnish (NFE)

AF:

0.0000447

AC:

AN:

44785

Other (OTH)

AF:

0.00

AC:

AN:

1152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.018

(source)

DANN

Benign

0.58

PhyloP100

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over