Variant 1-9245386-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H6PD	NM_004285.4 linkuse as main transcript	c.452A>C	p.Asp151Ala	missense_variant	2/5	ENST00000377403.7	NP_004276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H6PD	ENST00000377403.7 linkuse as main transcript	c.452A>C	p.Asp151Ala	missense_variant	2/5	1	NM_004285.4	ENSP00000366620	P1	O95479-1
H6PD	ENST00000602477.1 linkuse as main transcript	c.485A>C	p.Asp162Ala	missense_variant	2/5	1		ENSP00000473348		O95479-2

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

GnomAD3 exomes

AF:

0.118

AC:

29595

AN:

251168

Hom.:

2159

AF XY:

0.125

AC XY:

17023

AN XY:

135824

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 SAS exome

AF:

0.147

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

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.0834

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.105

AC:

15917

AN:

152242

Hom.:

1128

Cov.:

AF XY:

0.103

AC XY:

7682

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0255

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.140

Hom.:

2627

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.73

D;D

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.00021

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.5

D;.

REVEL

Uncertain

0.56

Sift

Benign

0.041

D;.

Sift4G

Benign

0.61

T;T

Polyphen

0.70

P;.

Vest4

0.17

MPC

0.23

ClinPred

0.034

GERP RS

4.2

Varity_R

0.32

gMVP

0.52

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

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