NM_004285.4:c.452A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004285.4(H6PD):c.452A>C(p.Asp151Ala) variant causes a missense change. The variant allele was found at a frequency of 0.137 in 1,614,012 control chromosomes in the GnomAD database, including 16,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1128 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15267 hom. )

Consequence

H6PD
NM_004285.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.79

Publications

29 publications found

Variant links:

Genes affected

H6PD (HGNC:4795): (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) There are 2 forms of glucose-6-phosphate dehydrogenase. G form is X-linked and H form, encoded by this gene, is autosomally linked. This H form shows activity with other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but H form is not found in red cells. [provided by RefSeq, Jul 2008]

H6PD Gene-Disease associations (from GenCC):

cortisone reductase deficiency 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
cortisone reductase deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

H6PD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024963915).

BP6

Variant 1-9245386-A-C is Benign according to our data. Variant chr1-9245386-A-C is described in ClinVar as Benign. ClinVar VariationId is 1601522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	NM_004285.4	MANE Select	c.452A>C	p.Asp151Ala	missense	Exon 2 of 5	NP_004276.2
	H6PD	NM_001282587.2		c.485A>C	p.Asp162Ala	missense	Exon 2 of 5	NP_001269516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	ENST00000377403.7	TSL:1 MANE Select	c.452A>C	p.Asp151Ala	missense	Exon 2 of 5	ENSP00000366620.2
	H6PD	ENST00000602477.1	TSL:1	c.485A>C	p.Asp162Ala	missense	Exon 2 of 5	ENSP00000473348.1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15926

AN:

152124

Hom.:

1128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.118

AC:

29595

AN:

251168

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0803

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.140

AC:

204862

AN:

1461770

Hom.:

15267

Cov.:

AF XY:

0.142

AC XY:

103089

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.0204

AC:

682

AN:

33480

American (AMR)

AF:

0.0834

AC:

3729

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3315

AN:

26134

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.148

AC:

12769

AN:

86252

European-Finnish (FIN)

AF:

0.121

AC:

6440

AN:

53392

Middle Eastern (MID)

AF:

0.164

AC:

948

AN:

5768

European-Non Finnish (NFE)

AF:

0.152

AC:

169155

AN:

1111924

Other (OTH)

AF:

0.129

AC:

7813

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

10911

21823

32734

43646

54557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5776

11552

17328

23104

28880

<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:

0.105

AC:

15917

AN:

152242

Hom.:

1128

Cov.:

AF XY:

0.103

AC XY:

7682

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0255

AC:

1060

AN:

41566

American (AMR)

AF:

0.106

AC:

1622

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

450

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5176

South Asian (SAS)

AF:

0.141

AC:

682

AN:

4830

European-Finnish (FIN)

AF:

0.111

AC:

1180

AN:

10608

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10461

AN:

67976

Other (OTH)

AF:

0.118

AC:

249

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

719

1437

2156

2874

3593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<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:

0.138

Hom.:

3447

Bravo

AF:

0.0986

TwinsUK

AF:

0.147

AC:

546

ALSPAC

AF:

0.139

AC:

536

ESP6500AA

AF:

0.0272

AC:

120

ESP6500EA

AF:

0.152

AC:

1307

ExAC

AF:

0.120

AC:

14571

Asia WGS

AF:

0.0650

AC:

229

AN:

3478

EpiCase

AF:

0.165

EpiControl

AF:

0.160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

PhyloP100

5.8

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.56

Sift

Benign

0.041

Sift4G

Benign

0.61

Polyphen

0.70

Vest4

0.17

MPC

0.23

ClinPred

0.034

GERP RS

4.2

Varity_R

0.32

gMVP

0.52

Mutation Taster

=96/4

polymorphism (auto)

(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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over