Variant X-154531643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001360016.2(G6PD):c.*357G>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 0.7 in 217,608 control chromosomes in the GnomAD database, including 44,702 homozygotes. There are 44,015 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 0.64 ( 19960 hom., 20634 hem., cov: 22)

Exomes 𝑓: 0.76 ( 24742 hom. 23381 hem. )

Consequence

G6PD
NM_001360016.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
G6PD	NM_001360016.2 linkuse as main transcript	c.*357G>A	3_prime_UTR_variant	13/13	ENST00000393562.10
G6PD	NM_000402.4 linkuse as main transcript	c.*357G>A	3_prime_UTR_variant	13/13
G6PD	NM_001042351.3 linkuse as main transcript	c.*357G>A	3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10 linkuse as main transcript	c.*357G>A		3_prime_UTR_variant	13/13	1	NM_001360016.2	P4	P11413-1

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

70534

AN:

109963

Hom.:

19963

Cov.:

AF XY:

0.640

AC XY:

20614

AN XY:

32221

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.521

Gnomad FIN

AF:

0.919

Gnomad MID

AF:

0.682

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.654

GnomAD4 exome

AF:

0.760

AC:

81727

AN:

107595

Hom.:

24742

Cov.:

AF XY:

0.718

AC XY:

23381

AN XY:

32581

show subpopulations

Gnomad4 AFR exome

AF:

0.0900

Gnomad4 AMR exome

AF:

0.731

Gnomad4 ASJ exome

AF:

0.706

Gnomad4 EAS exome

AF:

0.855

Gnomad4 SAS exome

AF:

0.576

Gnomad4 FIN exome

AF:

0.898

Gnomad4 NFE exome

AF:

0.845

Gnomad4 OTH exome

AF:

0.733

GnomAD4 genome

AF:

0.641

AC:

70540

AN:

110013

Hom.:

19960

Cov.:

AF XY:

0.639

AC XY:

20634

AN XY:

32281

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.727

Gnomad4 ASJ

AF:

0.769

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.919

Gnomad4 NFE

AF:

0.862

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.828

Hom.:

43571

Bravo

AF:

0.618

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Dunham Lab, University of Washington

Aug 12, 2022

Variant found in hemizygote with deficiency and anemia (PP4). Decreased activity in red blood cells (8-23%) (PS3). Predicted to alter mRNA secondary structure and alter miRNA binding sites (PP3). Individuals with variant on 1311C>T/1365-13T>C haplotype have deficiency, some with anemia; this haplotype alone was found to have decreased G6PD activity (10-60%) (BP5). Frequency of 32.1% gnomAD2 and 35.9% gnomAD3 (BA1). Reported as benign by ARUP Laboratories and Invitae (BP6). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.084

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

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