rs12916999

Variant names:

• chr15-78534570-C-T
• rs12916999
• NM_001013619.4:c.*900C>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.*900C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,084 control chromosomes in the GnomAD database, including 8,579 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 0.32 (8577 hom., cov: 31)
  • Exomes 𝑓: 0.29 (2 hom.)
• Consequence: HYKK NM_001013619.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.*900C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.662-2730C>T		intron_variant	Intron 4 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.*900C>T		3_prime_UTR_variant	Exon 5 of 5	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000569878.5	c.*900C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000455459.1
HYKK	ENST00000408962.6	c.662-2730C>T		intron_variant	Intron 4 of 4	5		ENSP00000386197.2
HYKK	ENST00000563233.2	c.662-2730C>T		intron_variant	Intron 3 of 3	2		ENSP00000454850.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47933 AN: 151940 Hom.: 8579 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.292 AC: 7 AN: 24 Hom.: 2 Cov.: 0 AF XY: 0.375 AC XY: 6 AN XY: 16

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.286 AC: 4 AN: 14

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.315 AC: 47944 AN: 152060 Hom.: 8577 Cov.: 31 AF XY: 0.313 AC XY: 23227 AN XY: 74320

African (AFR) AF: 0.163 AC: 6745 AN: 41480

American (AMR) AF: 0.250 AC: 3813 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3472

East Asian (EAS) AF: 0.165 AC: 855 AN: 5178

South Asian (SAS) AF: 0.345 AC: 1665 AN: 4822

European-Finnish (FIN) AF: 0.370 AC: 3907 AN: 10556

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28604 AN: 67972

Other (OTH) AF: 0.317 AC: 670 AN: 2112

Alfa AF: 0.329 Hom.: 1998

Bravo AF: 0.299

Asia WGS AF: 0.274 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.89
PhyloP100		-0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12916999; hg19: chr15-78826912;