rs7163730

Variant names:

• chr15-78522339-A-G
• rs7163730
• NM_001013619.4:c.478-5041A>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.478-5041A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,984 control chromosomes in the GnomAD database, including 5,878 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 (5878 hom., cov: 30)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• Publications: 27 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.478-5041A>G		intron_variant	Intron 3 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.478-5041A>G		intron_variant	Intron 3 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.478-5041A>G		intron_variant	Intron 3 of 4	5	NM_001013619.4	ENSP00000373640.4

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39611 AN: 151864 Hom.: 5863 Cov.: 30

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.261 AC: 39644 AN: 151984 Hom.: 5878 Cov.: 30 AF XY: 0.269 AC XY: 19996 AN XY: 74262

African (AFR) AF: 0.224 AC: 9289 AN: 41464

American (AMR) AF: 0.463 AC: 7062 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2084 AN: 5166

South Asian (SAS) AF: 0.391 AC: 1882 AN: 4810

European-Finnish (FIN) AF: 0.281 AC: 2953 AN: 10524

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14760 AN: 67986

Other (OTH) AF: 0.278 AC: 584 AN: 2100

Alfa AF: 0.239 Hom.: 18035

Bravo AF: 0.271

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.70
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: rs7163730; hg19: chr15-78814681;