NM_001358263.1:c.388-901G>A

Variant names:

• chr10-69363882-G-A
• rs3829183
• NM_001358263.1:c.388-901G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358263.1(HK1):​c.388-901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,098 control chromosomes in the GnomAD database, including 13,729 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13729 hom., cov: 32)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with visual defects and brain anomalies

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa 79

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• non-spherocytic hemolytic anemia due to hexokinase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Charcot-Marie-Tooth disease type 4G

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1	c.388-901G>A		intron_variant	Intron 6 of 20	ENST00000643399.2	NP_001345192.1
HK1	NM_000188.3	c.376-901G>A		intron_variant	Intron 3 of 17	ENST00000359426.7	NP_000179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.388-901G>A		intron_variant	Intron 6 of 20		NM_001358263.1	ENSP00000494664.1
HK1	ENST00000359426.7	c.376-901G>A		intron_variant	Intron 3 of 17	1	NM_000188.3	ENSP00000352398.6

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62128 AN: 151980 Hom.: 13700 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62207 AN: 152098 Hom.: 13729 Cov.: 32 AF XY: 0.412 AC XY: 30616 AN XY: 74338

African (AFR) AF: 0.571 AC: 23673 AN: 41486

American (AMR) AF: 0.312 AC: 4765 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1362 AN: 5180

South Asian (SAS) AF: 0.405 AC: 1951 AN: 4822

European-Finnish (FIN) AF: 0.487 AC: 5144 AN: 10572

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23325 AN: 67968

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.359 Hom.: 9304

Bravo AF: 0.401

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.015
DANN	Benign	0.53
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3829183; hg19: chr10-71123638;