chr5-176896297-G-T

Variant names:

• chr5-176896297-G-T
• rs691141
• NM_002115.3:c.-26-112C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002115.3(HK3):​c.-26-112C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000593 in 505,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: HK3 NM_002115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 17 publications found

Genes affected

HK3 (HGNC:4925): (hexokinase 3) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 3. Similar to hexokinases 1 and 2, this allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK3	NM_002115.3	c.-26-112C>A		intron_variant	Intron 1 of 18	ENST00000292432.10	NP_002106.2
HK3	XM_047417134.1	c.-26-112C>A		intron_variant	Intron 1 of 17		XP_047273090.1
HK3	XM_011534540.3	c.-26-112C>A		intron_variant	Intron 1 of 13		XP_011532842.1
HK3	XR_941102.3	n.81-112C>A		intron_variant	Intron 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK3	ENST00000292432.10	c.-26-112C>A		intron_variant	Intron 1 of 18	1	NM_002115.3	ENSP00000292432.5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000565 AC: 2 AN: 354058 Hom.: 0 AF XY: 0.00000544 AC XY: 1 AN XY: 183814

African (AFR) AF: 0.00 AC: 0 AN: 8566

American (AMR) AF: 0.00 AC: 0 AN: 10948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10810

East Asian (EAS) AF: 0.00 AC: 0 AN: 24034

South Asian (SAS) AF: 0.00 AC: 0 AN: 24276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2094

European-Non Finnish (NFE) AF: 0.00000929 AC: 2 AN: 215220

Other (OTH) AF: 0.00 AC: 0 AN: 20414

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74186

African (AFR) AF: 0.00 AC: 0 AN: 41342

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 13163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.38
DANN	Benign	0.74
PhyloP100		-0.79

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: rs691141; hg19: chr5-176323298;