Variant chr10-69300866-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001358263.1(HK1):c.75+5186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,453,568 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 11 hom. )

Consequence

HK1
NM_001358263.1 intron

Scores

Splicing: ADA: 0.00001029

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.70

Variant links:

Genes affected

HK1 (HGNC:4922): (hexokinase 1) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]

HK1 links:

RPS15AP28 (HGNC:36381): (ribosomal protein S15a pseudogene 28)

RPS15AP28 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 10-69300866-G-A is Benign according to our data. Variant chr10-69300866-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1330405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.001 (1301/1301310) while in subpopulation SAS AF= 0.0127 (1052/82554). AF 95% confidence interval is 0.0121. There are 11 homozygotes in gnomad4_exome. There are 940 alleles in male gnomad4_exome subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_001358263.1 linkuse as main transcript	c.75+5186G>A		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000643399.2 linkuse as main transcript	c.75+5186G>A		intron_variant			NM_001358263.1		P19367-3
RPS15AP28	ENST00000435088.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00165

AC:

392

AN:

237744

Hom.:

AF XY:

0.00233

AC XY:

300

AN XY:

128494

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.0000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000286

Gnomad SAS exome

AF:

0.0116

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000330

Gnomad OTH exome

AF:

0.000679

GnomAD4 exome

AF:

0.00100

AC:

1301

AN:

1301310

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

940

AN XY:

654958

show subpopulations

Gnomad4 AFR exome

AF:

0.000165

Gnomad4 AMR exome

AF:

0.000117

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000177

Gnomad4 OTH exome

AF:

0.000837

GnomAD4 genome

AF:

0.000539

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000344

Hom.:

Bravo

AF:

0.000280

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	HK1: PP3, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000010

dbscSNV1_RF

Benign

0.0080

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