15-78525105-A-T

Variant names:

• chr15-78525105-A-T
• rs4461039
• NM_001013619.4:c.478-2275A>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.478-2275A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,092 control chromosomes in the GnomAD database, including 6,397 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 0.27 (6397 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.459 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	NM_001013619.4	MANE Select	c.478-2275A>T		intron	N/A	NP_001013641.2
	HYKK	NM_001083612.2		c.478-2275A>T		intron	N/A	NP_001077081.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	ENST00000388988.9	TSL:5 MANE Select	c.478-2275A>T		intron	N/A	ENSP00000373640.4
	HYKK	ENST00000566332.5	TSL:1	c.478-2275A>T		intron	N/A	ENSP00000457154.1
	HYKK	ENST00000569878.5	TSL:5	c.478-2275A>T		intron	N/A	ENSP00000455459.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41700 AN: 151972 Hom.: 6382 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.274 AC: 41746 AN: 152092 Hom.: 6397 Cov.: 32 AF XY: 0.282 AC XY: 20987 AN XY: 74370

African (AFR) AF: 0.270 AC: 11212 AN: 41482

American (AMR) AF: 0.468 AC: 7145 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2087 AN: 5166

South Asian (SAS) AF: 0.388 AC: 1869 AN: 4822

European-Finnish (FIN) AF: 0.281 AC: 2977 AN: 10588

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14795 AN: 67984

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.134 Hom.: 217

Bravo AF: 0.286

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.15
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: rs4461039; hg19: chr15-78817447;