Variant 1-9264154-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004285.4(H6PD):c.1661C>T(p.Pro554Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,612,930 control chromosomes in the GnomAD database, including 12,345 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. Synonymous variant affecting the same amino acid position (i.e. P554P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.090 ( 845 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11500 hom. )

Consequence

H6PD
NM_004285.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016513467).

BP6

Variant 1-9264154-C-T is Benign according to our data. Variant chr1-9264154-C-T is described in ClinVar as [Benign]. Clinvar id is 1600034.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4 linkuse as main transcript	c.1661C>T	p.Pro554Leu	missense_variant	5/5	ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7 linkuse as main transcript	c.1661C>T	p.Pro554Leu	missense_variant	5/5	1	NM_004285.4	P1	O95479-1
H6PD	ENST00000602477.1 linkuse as main transcript	c.1694C>T	p.Pro565Leu	missense_variant	5/5	1			O95479-2

Frequencies

GnomAD3 genomes

AF:

0.0906

AC:

13777

AN:

152126

Hom.:

845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0904

Gnomad EAS

AF:

0.0615

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0890

GnomAD3 exomes

AF:

0.117

AC:

29045

AN:

248784

Hom.:

1999

AF XY:

0.122

AC XY:

16468

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0888

Gnomad EAS exome

AF:

0.0555

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.0724

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.122

AC:

177688

AN:

1460686

Hom.:

11500

Cov.:

AF XY:

0.124

AC XY:

89860

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.0889

Gnomad4 EAS exome

AF:

0.0580

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.0761

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0904

AC:

13766

AN:

152244

Hom.:

845

Cov.:

AF XY:

0.0902

AC XY:

6713

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.0904

Gnomad4 EAS

AF:

0.0616

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.0881

Alfa

AF:

0.116

Hom.:

2367

Bravo

AF:

0.0889

TwinsUK

AF:

0.121

AC:

450

ALSPAC

AF:

0.122

AC:

471

ESP6500AA

AF:

0.0227

AC:

100

ESP6500EA

AF:

0.123

AC:

1054

ExAC

AF:

0.115

AC:

14010

Asia WGS

AF:

0.108

AC:

374

AN:

3478

EpiCase

AF:

0.127

EpiControl

AF:

0.122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.39

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.00040

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.7

D;.

REVEL

Uncertain

0.39

Sift

Benign

0.033

D;.

Sift4G

Benign

0.13

T;T

Polyphen

0.91

P;.

Vest4

0.13

MPC

0.11

ClinPred

0.020

GERP RS

4.8

Varity_R

0.080

gMVP

0.58

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