rs9788682

chr15-78510244-G-Achr15-78510244-G-T

Variant summary

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

The NM_001013619.4(HYKK):c.-6+2573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,152 control chromosomes in the GnomAD database, including 4,316 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 0.22 (4316 hom., cov: 29)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.-6+2573G>A		intron_variant		ENST00000388988.9
HYKK	NM_001083612.2	c.-6+2573G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.-6+2573G>A		intron_variant		5	NM_001013619.4	P1
HYKK	ENST00000566332.5	c.-6+2573G>A		intron_variant		1
HYKK	ENST00000408962.6	c.-6+2573G>A		intron_variant		5
HYKK	ENST00000566289.5	c.-6+2573G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 33947 AN: 151038 Hom.: 4309 Cov.: 29

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.225 AC: 33968 AN: 151152 Hom.: 4316 Cov.: 29 AF XY: 0.232 AC XY: 17124 AN XY: 73806

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.234

Alfa AF: 0.133 Hom.: 292

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.5
Dann	Benign	0.75

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: rs9788682; hg19: chr15-78802586;