rs10519203

Variant names:

• chr15-78521704-G-A
• rs10519203
• NM_001013619.4:c.478-5676G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78521704-G-A
• chr15-78521704-G-C
• chr15-78521704-G-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.478-5676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,862 control chromosomes in the GnomAD database, including 35,258 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 0.68 (35258 hom., cov: 30)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 64 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.478-5676G>A		intron_variant	Intron 3 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.478-5676G>A		intron_variant	Intron 3 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.478-5676G>A		intron_variant	Intron 3 of 4	5	NM_001013619.4	ENSP00000373640.4

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102979 AN: 151746 Hom.: 35226 Cov.: 30

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.679 AC: 103060 AN: 151862 Hom.: 35258 Cov.: 30 AF XY: 0.685 AC XY: 50819 AN XY: 74240

African (AFR) AF: 0.677 AC: 28005 AN: 41378

American (AMR) AF: 0.748 AC: 11413 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2232 AN: 3468

East Asian (EAS) AF: 0.906 AC: 4657 AN: 5140

South Asian (SAS) AF: 0.760 AC: 3646 AN: 4800

European-Finnish (FIN) AF: 0.667 AC: 7045 AN: 10562

Middle Eastern (MID) AF: 0.586 AC: 170 AN: 290

European-Non Finnish (NFE) AF: 0.647 AC: 43938 AN: 67950

Other (OTH) AF: 0.674 AC: 1423 AN: 2112

Alfa AF: 0.671 Hom.: 63544

Bravo AF: 0.684

Asia WGS AF: 0.827 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.58
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: rs10519203; hg19: chr15-78814046;