5-176896297-G-C

Variant names:

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

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>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 354,058 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: HK3 NM_002115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 0 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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002115.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK3	NM_002115.3	MANE Select	c.-26-112C>G		intron	N/A	NP_002106.2	P52790

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK3	ENST00000292432.10	TSL:1 MANE Select	c.-26-112C>G		intron	N/A	ENSP00000292432.5	P52790
	HK3	ENST00000874508.1		c.-26-112C>G		intron	N/A	ENSP00000544567.1
	HK3	ENST00000970949.1		c.-26-112C>G		intron	N/A	ENSP00000641008.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000282 AC: 1 AN: 354058 Hom.: 0 AF XY: 0.00000544 AC XY: 1 AN XY: 183816

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 AN: 10950

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: 0.00000465 AC: 1 AN: 215218

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.77
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;