15-78510244-G-T

Variant names:

• chr15-78510244-G-T
• rs9788682
• NM_001013619.4:c.-6+2573G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013619.4(HYKK):​c.-6+2573G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 151,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0012 (0 hom., cov: 29)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 19 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.-6+2573G>T		intron	N/A	NP_001013641.2	A2RU49-1
	HYKK	NM_001083612.2		c.-6+2573G>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.-6+2573G>T		intron	N/A	ENSP00000373640.4	A2RU49-1
	HYKK	ENST00000566332.5	TSL:1	c.-6+2573G>T		intron	N/A	ENSP00000457154.1	A0A0C4DGM4
	HYKK	ENST00000408962.6	TSL:5	c.-6+2573G>T		intron	N/A	ENSP00000386197.2	A2RU49-3

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 181 AN: 151136 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000969

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

GnomAD4 genome AF: 0.00120 AC: 181 AN: 151250 Hom.: 0 Cov.: 29 AF XY: 0.00123 AC XY: 91 AN XY: 73850

African (AFR) AF: 0.00282 AC: 116 AN: 41164

American (AMR) AF: 0.000328 AC: 5 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67842

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.00 Hom.: 292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		0.61

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: rs9788682; hg19: chr15-78802586;