rs952216

Variant names:

• chr15-78526860-C-T
• rs952216
• NM_001013619.4:c.478-520C>T

Variant summary

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

The NM_001013619.4(HYKK):​c.478-520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,048 control chromosomes in the GnomAD database, including 8,509 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 0.31 (8509 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.478-520C>T		intron_variant	Intron 3 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.478-520C>T		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.478-520C>T		intron_variant	Intron 3 of 4	5	NM_001013619.4	ENSP00000373640.4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47615 AN: 151930 Hom.: 8513 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.313 AC: 47625 AN: 152048 Hom.: 8509 Cov.: 32 AF XY: 0.310 AC XY: 23069 AN XY: 74298

African (AFR) AF: 0.156 AC: 6481 AN: 41510

American (AMR) AF: 0.249 AC: 3805 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1229 AN: 3468

East Asian (EAS) AF: 0.164 AC: 851 AN: 5174

South Asian (SAS) AF: 0.346 AC: 1666 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3896 AN: 10532

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28575 AN: 67948

Other (OTH) AF: 0.317 AC: 669 AN: 2112

Alfa AF: 0.357 Hom.: 1399

Bravo AF: 0.297

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.7
DANN	Benign	0.68
PhyloP100		-0.0080
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: rs952216; hg19: chr15-78819202;