rs5030949

Variant names:

• chr10-69278584-C-A
• rs5030949
• NM_001358263.1:c.-397C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-69278584-C-A
• chr10-69278584-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001358263.1(HK1):​c.-397C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,060 control chromosomes in the GnomAD database, including 6,064 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 0.26 (6062 hom., cov: 32)
  • Exomes 𝑓: 0.41 (2 hom.)
• Consequence: HK1 NM_001358263.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1	c.-397C>A		5_prime_UTR_variant	Exon 1 of 21	ENST00000643399.2	NP_001345192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.-397C>A		5_prime_UTR_variant	Exon 1 of 21		NM_001358263.1	ENSP00000494664.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39756 AN: 151920 Hom.: 6061 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.409 AC: 9 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.444 AC: 8 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.262 AC: 39760 AN: 152038 Hom.: 6062 Cov.: 32 AF XY: 0.263 AC XY: 19557 AN XY: 74300

African (AFR) AF: 0.124 AC: 5138 AN: 41510

American (AMR) AF: 0.408 AC: 6221 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2855 AN: 5142

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2612 AN: 10554

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19644 AN: 67968

Other (OTH) AF: 0.306 AC: 646 AN: 2110

Alfa AF: 0.289 Hom.: 27473

Bravo AF: 0.273

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		1.8
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5030949; hg19: chr10-71038340;