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GeneBe

1-9245189-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars. Variant chr1-9245189-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.76 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
H6PDNM_004285.4 linkuse as main transcriptc.255C>T p.Ser85= synonymous_variant 2/5 ENST00000377403.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
H6PDENST00000377403.7 linkuse as main transcriptc.255C>T p.Ser85= synonymous_variant 2/51 NM_004285.4 P1O95479-1
H6PDENST00000602477.1 linkuse as main transcriptc.288C>T p.Ser96= synonymous_variant 2/51 O95479-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00197
AC:
300
AN:
152236
Hom.:
2
Cov.:
33
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.:
10
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.:
27
Cov.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00197
AC:
300
AN:
152354
Hom.:
2
Cov.:
33
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.:
3
Bravo
AF:
0.00157
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.00294
EpiControl
AF:
0.00261

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 submitterclinical testingInvitaeDec 22, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
Cadd
Benign
14
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.

Other links and lift over

dbSNP: rs138775586; hg19: chr1-9305248; COSMIC: COSV66232642; API