15-78510715-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.-5-2369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,002 control chromosomes in the GnomAD database, including 8,847 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 (8847 hom., cov: 31)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.-5-2369C>T		intron_variant		ENST00000388988.9
HYKK	NM_001083612.2	c.-5-2369C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.-5-2369C>T		intron_variant		5	NM_001013619.4	P1
HYKK	ENST00000566332.5	c.-5-2369C>T		intron_variant		1
HYKK	ENST00000408962.6	c.-5-2369C>T		intron_variant		5
HYKK	ENST00000566289.5	c.-5-2369C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48723 AN: 151880 Hom.: 8827 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.321 AC: 48766 AN: 152002 Hom.: 8847 Cov.: 31 AF XY: 0.329 AC XY: 24440 AN XY: 74294

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.321

Alfa AF: 0.323 Hom.: 1901

Bravo AF: 0.339

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.41
Dann	Benign	0.26

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: rs7164594; hg19: chr15-78803057;