15-78510715-C-T

Variant names:

• chr15-78510715-C-T
• rs7164594
• NM_001013619.4:c.-5-2369C>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.-5-2369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,002 control chromosomes in the GnomAD database, including 8,847 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 (8847 hom., cov: 31)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 30 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013619.4. 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
	HYKK	NM_001013619.4	MANE Select	c.-5-2369C>T		intron	N/A	NP_001013641.2	A2RU49-1
	HYKK	NM_001083612.2		c.-5-2369C>T		intron	N/A	NP_001077081.1	A2RU49-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	ENST00000388988.9	TSL:5 MANE Select	c.-5-2369C>T		intron	N/A	ENSP00000373640.4	A2RU49-1
	HYKK	ENST00000566332.5	TSL:1	c.-5-2369C>T		intron	N/A	ENSP00000457154.1	A0A0C4DGM4
	HYKK	ENST00000408962.6	TSL:5	c.-5-2369C>T		intron	N/A	ENSP00000386197.2	A2RU49-3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48723 AN: 151880 Hom.: 8827 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.321 AC: 48766 AN: 152002 Hom.: 8847 Cov.: 31 AF XY: 0.329 AC XY: 24440 AN XY: 74294

African (AFR) AF: 0.409 AC: 16967 AN: 41436

American (AMR) AF: 0.484 AC: 7384 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3468

East Asian (EAS) AF: 0.525 AC: 2710 AN: 5164

South Asian (SAS) AF: 0.413 AC: 1992 AN: 4828

European-Finnish (FIN) AF: 0.279 AC: 2945 AN: 10552

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14928 AN: 67990

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.328 Hom.: 2223

Bravo AF: 0.339

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.26
PhyloP100		-0.30
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: rs7164594; hg19: chr15-78803057;