rs931794

Positions:

• chr15-78533838-G-A
• chr15-78533838-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013619.4(HYKK):​c.*168G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 590,018 control chromosomes in the GnomAD database, including 134,807 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 0.69 (36603 hom., cov: 32)
  • Exomes 𝑓: 0.67 (98204 hom.)
• Consequence: HYKK NM_001013619.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.*168G>A		3_prime_UTR_variant	5/5	ENST00000388988.9
HYKK	NM_001083612.2	c.662-3462G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.*168G>A		3_prime_UTR_variant	5/5	5	NM_001013619.4	P1
HYKK	ENST00000569878.5	c.*168G>A		3_prime_UTR_variant	4/4	5		P1
HYKK	ENST00000408962.6	c.662-3462G>A		intron_variant		5
HYKK	ENST00000563233.2	c.662-3462G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105018 AN: 151954 Hom.: 36564 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.668 AC: 292427 AN: 437946 Hom.: 98204 Cov.: 4 AF XY: 0.672 AC XY: 154495 AN XY: 229922

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.630

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.691 AC: 105111 AN: 152072 Hom.: 36603 Cov.: 32 AF XY: 0.696 AC XY: 51707 AN XY: 74336

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.681

Alfa AF: 0.658 Hom.: 35041

Bravo AF: 0.699

Asia WGS AF: 0.740 AC: 2572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs931794; hg19: chr15-78826180;