rs16969914

Variant names:

• chr15-78509414-T-G
• rs16969914
• NM_001013619.4:c.-6+1743T>G

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+1743T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00852 in 152,310 control chromosomes in the GnomAD database, including 117 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 0.0085 (117 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.-6+1743T>G		intron_variant	Intron 1 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.-6+1743T>G		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+1743T>G		intron_variant	Intron 1 of 4	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000566332.5	c.-6+1743T>G		intron_variant	Intron 1 of 3	1		ENSP00000457154.1
HYKK	ENST00000408962.6	c.-6+1743T>G		intron_variant	Intron 1 of 4	5		ENSP00000386197.2
HYKK	ENST00000566289.5	n.-6+1743T>G		intron_variant	Intron 1 of 4	2		ENSP00000456614.1

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1300 AN: 152192 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00764

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

GnomAD4 genome AF: 0.00852 AC: 1298 AN: 152310 Hom.: 117 Cov.: 32 AF XY: 0.00955 AC XY: 711 AN XY: 74486

African (AFR) AF: 0.00111 AC: 46 AN: 41584

American (AMR) AF: 0.00131 AC: 20 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5160

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00322 Hom.: 25

Bravo AF: 0.00974

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.4
DANN	Benign	0.70
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs16969914; hg19: chr15-78801756;