rs4380026

Positions:

• chr15-78518603-G-A

Variant summary

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

The NM_001013619.4(HYKK):​c.477+3496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 455,482 control chromosomes in the GnomAD database, including 364 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 0.034 (293 hom., cov: 31)
  • Exomes 𝑓: 0.0052 (71 hom.)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.477+3496G>A		intron_variant		ENST00000388988.9
HYKK	NM_001083612.2	c.477+3496G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.477+3496G>A		intron_variant		5	NM_001013619.4	P1

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5155 AN: 151992 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0235

GnomAD3 exomes AF: 0.00849 AC: 1139 AN: 134236 Hom.: 55 AF XY: 0.00706 AC XY: 516 AN XY: 73136

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.00620

Gnomad ASJ exome AF: 0.0185

Gnomad EAS exome AF: 0.0000954

Gnomad SAS exome AF: 0.000445

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000645

Gnomad OTH exome AF: 0.00436

GnomAD4 exome AF: 0.00518 AC: 1572 AN: 303372 Hom.: 71 Cov.: 0 AF XY: 0.00403 AC XY: 696 AN XY: 172846

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.00635

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.000109

Gnomad4 SAS exome AF: 0.000352

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000321

Gnomad4 OTH exome AF: 0.00756

GnomAD4 genome AF: 0.0339 AC: 5161 AN: 152110 Hom.: 293 Cov.: 31 AF XY: 0.0334 AC XY: 2482 AN XY: 74356

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00786 Hom.: 46

Bravo AF: 0.0381

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.30
DANN	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs4380026; hg19: chr15-78810945;