15-78508152-C-T

Variant names:

• chr15-78508152-C-T
• rs7168796
• NM_001013619.4:c.-6+481C>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.-6+481C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,252 control chromosomes in the GnomAD database, including 69,258 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 0.95 (69258 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.-6+481C>T		intron_variant	Intron 1 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.-6+481C>T		intron_variant	Intron 1 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.-6+481C>T		intron_variant	Intron 1 of 4	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000566332.5	c.-6+481C>T		intron_variant	Intron 1 of 3	1		ENSP00000457154.1
HYKK	ENST00000408962.6	c.-6+481C>T		intron_variant	Intron 1 of 4	5		ENSP00000386197.2
HYKK	ENST00000566289.5	n.-6+481C>T		intron_variant	Intron 1 of 4	2		ENSP00000456614.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144606 AN: 152134 Hom.: 69217 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.971

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

GnomAD4 genome AF: 0.950 AC: 144707 AN: 152252 Hom.: 69258 Cov.: 32 AF XY: 0.953 AC XY: 70969 AN XY: 74452

African (AFR) AF: 0.826 AC: 34293 AN: 41494

American (AMR) AF: 0.984 AC: 15065 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3462 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68009 AN: 68038

Other (OTH) AF: 0.972 AC: 2046 AN: 2106

Alfa AF: 0.977 Hom.: 37722

Bravo AF: 0.942

Asia WGS AF: 0.990 AC: 3444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.65
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7168796; hg19: chr15-78800494;