rs3216174

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_001360016.2(G6PD):c.486-34delT 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

Publications

6 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: Benign. The variant received -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 submission is: [Conflicting_classifications_of_pathogenicity].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
G6PD	NM_001360016.2 link	c.486-34delT	intron_variant	Intron 5 of 12	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4 link	c.576-34delT	intron_variant	Intron 5 of 12		NP_000393.4	P11413-3
G6PD	NM_001042351.3 link	c.486-34delT	intron_variant	Intron 5 of 12		NP_001035810.1	P11413-1A0A384NL00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10 link	c.486-34delT		intron_variant	Intron 5 of 12	1	NM_001360016.2	ENSP00000377192.3		P11413-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

398

AN:

112098

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00889

AC:

1586

AN:

178413

AF XY:

0.00758

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 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

African (AFR)

AF:

0.00

AC:

AN:

26356

American (AMR)

AF:

0.000284

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.000258

AC:

AN:

19367

East Asian (EAS)

AF:

0.0964

AC:

2909

AN:

30189

South Asian (SAS)

AF:

0.000999

AC:

AN:

54051

European-Finnish (FIN)

AF:

0.0123

AC:

462

AN:

37654

Middle Eastern (MID)

AF:

0.000732

AC:

AN:

4097

European-Non Finnish (NFE)

AF:

0.000241

AC:

203

AN:

840607

Other (OTH)

AF:

0.00479

AC:

220

AN:

45977

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

148

296

443

591

739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00353

AC:

396

AN:

112152

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

148

AN XY:

34344

show subpopulations

African (AFR)

AF:

0.0000647

AC:

AN:

30908

American (AMR)

AF:

0.00

AC:

AN:

10712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.0846

AC:

297

AN:

3510

South Asian (SAS)

AF:

0.00146

AC:

AN:

2732

European-Finnish (FIN)

AF:

0.0119

AC:

AN:

6207

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000283

AC:

AN:

53000

Other (OTH)

AF:

0.00261

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Aug 12, 2022

Dunham Lab, University of Washington

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

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). -

Jan 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 20, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs3216174

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over