NM_004285.4:c.636G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004285.4(H6PD):c.636G>A(p.Ala212Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,606,590 control chromosomes in the GnomAD database, including 46,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3679 hom., cov: 31)

Exomes 𝑓: 0.24 ( 43179 hom. )

Consequence

H6PD
NM_004285.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.424

Publications

14 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-9246974-G-A is Benign according to our data. Variant chr1-9246974-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.424 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.636G>A	p.Ala212Ala	synonymous	Exon 3 of 5	NP_004276.2
	H6PD	NM_001282587.2		c.669G>A	p.Ala223Ala	synonymous	Exon 3 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.636G>A	p.Ala212Ala	synonymous	Exon 3 of 5	ENSP00000366620.2
	H6PD	ENST00000602477.1	TSL:1	c.669G>A	p.Ala223Ala	synonymous	Exon 3 of 5	ENSP00000473348.1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32048

AN:

151970

Hom.:

3678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.226

AC:

56934

AN:

251388

AF XY:

0.225

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.239

AC:

347434

AN:

1454502

Hom.:

43179

Cov.:

AF XY:

0.236

AC XY:

171090

AN XY:

724012

show subpopulations

African (AFR)

AF:

0.156

AC:

5197

AN:

33344

American (AMR)

AF:

0.236

AC:

10562

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4762

AN:

26088

East Asian (EAS)

AF:

0.400

AC:

15858

AN:

39638

South Asian (SAS)

AF:

0.152

AC:

13107

AN:

86136

European-Finnish (FIN)

AF:

0.162

AC:

8670

AN:

53380

Middle Eastern (MID)

AF:

0.214

AC:

1231

AN:

5754

European-Non Finnish (NFE)

AF:

0.248

AC:

273864

AN:

1105300

Other (OTH)

AF:

0.236

AC:

14183

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

12450

24899

37349

49798

62248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9366

18732

28098

37464

46830

<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:

0.211

AC:

32058

AN:

152088

Hom.:

3679

Cov.:

AF XY:

0.208

AC XY:

15487

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.155

AC:

6429

AN:

41502

American (AMR)

AF:

0.231

AC:

3530

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

598

AN:

3472

East Asian (EAS)

AF:

0.429

AC:

2205

AN:

5136

South Asian (SAS)

AF:

0.167

AC:

805

AN:

4830

European-Finnish (FIN)

AF:

0.151

AC:

1605

AN:

10606

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16080

AN:

67956

Other (OTH)

AF:

0.227

AC:

480

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1292

2584

3877

5169

6461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.233

Hom.:

12883

Bravo

AF:

0.220

Asia WGS

AF:

0.245

AC:

851

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 18, 2020

GeneDx

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

Cortisone reductase deficiency 1

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.68

(source)

DANN

Benign

0.70

PhyloP100

-0.42

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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