Variant chrX-154534529-GA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001360016.2(G6PD):c.486-34del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,205,636 control chromosomes in the GnomAD database, including 130 homozygotes. There are 1,325 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 12 hom., 148 hem., cov: 23)

Exomes 𝑓: 0.0035 ( 118 hom. 1177 hem. )

Consequence

G6PD
NM_001360016.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.169

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 -9 ACMG points.

BP6

Variant X-154534529-GA-G is Benign according to our data. Variant chrX-154534529-GA-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 439744.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
G6PD	NM_001360016.2 linkuse as main transcript	c.486-34del	intron_variant	ENST00000393562.10
G6PD	NM_000402.4 linkuse as main transcript	c.576-34del	intron_variant
G6PD	NM_001042351.3 linkuse as main transcript	c.486-34del	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10 linkuse as main transcript	c.486-34del		intron_variant		1	NM_001360016.2	P4	P11413-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

398

AN:

112098

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

147

AN XY:

34280

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0852

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000283

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.00889

AC:

1586

AN:

178413

Hom.:

AF XY:

0.00758

AC XY:

491

AN XY:

64805

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000256

Gnomad ASJ exome

AF:

0.000403

Gnomad EAS exome

AF:

0.0950

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00354

AC:

3866

AN:

1093484

Hom.:

118

Cov.:

AF XY:

0.00327

AC XY:

1177

AN XY:

360014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000284

Gnomad4 ASJ exome

AF:

0.000258

Gnomad4 EAS exome

AF:

0.0964

Gnomad4 SAS exome

AF:

0.000999

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.000241

Gnomad4 OTH exome

AF:

0.00479

GnomAD4 genome

AF:

0.00353

AC:

396

AN:

112152

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

148

AN XY:

34344

show subpopulations

Gnomad4 AFR

AF:

0.0000647

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0846

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.000283

Gnomad4 OTH

AF:

0.00261

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00418

Asia WGS

AF:

0.0290

AC:

AN:

2522

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 11, 2023	- -
Uncertain significance, criteria provided, single submitter	curation	Dunham Lab, University of Washington	Aug 12, 2022	Variant found in unrelated hemizygotes with deficiency (PS4_M, PP4). Decreased activity in red blood cells (PS3). Reported as benign by multiple clinical testing groups (BP6). Post_P 0.89997 (odds of pathogenicity 80.97, Prior_P 0.1). -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jan 20, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

This variant is associated with the following publications: (PMID: 30077011, 26829728) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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