15-78509054-A-C

Variant names:

• chr15-78509054-A-C
• rs9672189
• NM_001013619.4:c.-6+1383A>C

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+1383A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,054 control chromosomes in the GnomAD database, including 470 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 0.043 (470 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.-6+1383A>C		intron_variant	Intron 1 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.-6+1383A>C		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+1383A>C		intron_variant	Intron 1 of 4	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000566332.5	c.-6+1383A>C		intron_variant	Intron 1 of 3	1		ENSP00000457154.1
HYKK	ENST00000408962.6	c.-6+1383A>C		intron_variant	Intron 1 of 4	5		ENSP00000386197.2
HYKK	ENST00000566289.5	n.-6+1383A>C		intron_variant	Intron 1 of 4	2		ENSP00000456614.1

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6583 AN: 151940 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0433 AC: 6590 AN: 152054 Hom.: 470 Cov.: 32 AF XY: 0.0426 AC XY: 3163 AN XY: 74332

African (AFR) AF: 0.149 AC: 6177 AN: 41422

American (AMR) AF: 0.0153 AC: 234 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68006

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0377 Hom.: 40

Bravo AF: 0.0494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.52
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: rs9672189; hg19: chr15-78801396;