rs952216

chr15-78526860-C-T

Variant summary

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

The NM_001013619.4(HYKK):c.478-520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,048 control chromosomes in the GnomAD database, including 8,509 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 0.31 (8509 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.478-520C>T		intron_variant		ENST00000388988.9
HYKK	NM_001083612.2	c.478-520C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.478-520C>T		intron_variant		5	NM_001013619.4	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47615 AN: 151930 Hom.: 8513 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.313 AC: 47625 AN: 152048 Hom.: 8509 Cov.: 32 AF XY: 0.310 AC XY: 23069 AN XY: 74298

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.317

Alfa AF: 0.365 Hom.: 1389

Bravo AF: 0.297

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.7
Dann	Benign	0.68

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: rs952216; hg19: chr15-78819202;