rs12910289

Variant names:

• chr15-78529723-T-G
• rs12910289
• NM_001013619.4:c.661+2160T>G

Variant summary

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

The NM_001013619.4(HYKK):​c.661+2160T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,150 control chromosomes in the GnomAD database, including 8,566 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 0.32 (8566 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 11 publications found

Genes affected

HYKK (HGNC:34403): (hydroxylysine kinase) Enables hydroxylysine kinase activity. Predicted to be involved in lysine catabolic process. Predicted to be located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

HYKK Gene-Disease associations (from GenCC):

• inborn disorder of lysine and hydroxylysine metabolism

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.661+2160T>G		intron_variant	Intron 4 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.661+2160T>G		intron_variant	Intron 4 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.661+2160T>G		intron_variant	Intron 4 of 4	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000569878.5	c.661+2160T>G		intron_variant	Intron 3 of 3	5		ENSP00000455459.1
HYKK	ENST00000408962.6	c.661+2160T>G		intron_variant	Intron 4 of 4	5		ENSP00000386197.2
HYKK	ENST00000563233.2	c.661+2160T>G		intron_variant	Intron 3 of 3	2		ENSP00000454850.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47925 AN: 152032 Hom.: 8569 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.315 AC: 47934 AN: 152150 Hom.: 8566 Cov.: 32 AF XY: 0.312 AC XY: 23220 AN XY: 74386

African (AFR) AF: 0.162 AC: 6741 AN: 41532

American (AMR) AF: 0.250 AC: 3815 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3472

East Asian (EAS) AF: 0.165 AC: 856 AN: 5188

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4832

European-Finnish (FIN) AF: 0.369 AC: 3895 AN: 10564

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28603 AN: 67968

Other (OTH) AF: 0.318 AC: 673 AN: 2114

Alfa AF: 0.329 Hom.: 1994

Bravo AF: 0.300

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.76
PhyloP100		0.73
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: rs12910289; hg19: chr15-78822065;