Variant chr1-9245189-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004285.4(H6PD):c.255C>T(p.Ser85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,614,244 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 27 hom. )

Consequence

H6PD
NM_004285.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.76

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 1-9245189-C-T is Benign according to our data. Variant chr1-9245189-C-T is described in ClinVar as [Benign]. Clinvar id is 730928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-9245189-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00197 (300/152354) while in subpopulation SAS AF= 0.0188 (91/4832). AF 95% confidence interval is 0.0157. There are 2 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H6PD	NM_004285.4 linkuse as main transcript	c.255C>T	p.Ser85=	synonymous_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.255C>T	p.Ser85=	synonymous_variant	2/5	1	NM_004285.4	ENSP00000366620	P1	O95479-1
H6PD	ENST00000602477.1 linkuse as main transcript	c.288C>T	p.Ser96=	synonymous_variant	2/5	1		ENSP00000473348		O95479-2

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00368

AC:

926

AN:

251396

Hom.:

AF XY:

0.00436

AC XY:

593

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00270

AC:

3942

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2271

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0149

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00157

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

152354

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0188

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00157

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00261

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 22, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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