15-78522339-A-G

Position:

• chr15-78522339-A-G

Variant summary

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

The NM_001013619.4(HYKK):​c.478-5041A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,984 control chromosomes in the GnomAD database, including 5,878 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 0.26 (5878 hom., cov: 30)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.478-5041A>G		intron_variant		ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.478-5041A>G		intron_variant			NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.478-5041A>G		intron_variant		5	NM_001013619.4	ENSP00000373640	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39611 AN: 151864 Hom.: 5863 Cov.: 30

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.261 AC: 39644 AN: 151984 Hom.: 5878 Cov.: 30 AF XY: 0.269 AC XY: 19996 AN XY: 74262

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.278

Alfa AF: 0.234 Hom.: 7286

Bravo AF: 0.271

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.70

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: rs7163730; hg19: chr15-78814681;