15-78510527-C-T

Variant names:

• chr15-78510527-C-T
• rs9788721
• NM_001013619.4:c.-5-2557C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013619.4(HYKK):​c.-5-2557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,864 control chromosomes in the GnomAD database, including 32,554 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 0.65 (32554 hom., cov: 30)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 42 publications found

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]

HYKK Gene-Disease associations (from GenCC):

• inborn disorder of lysine and hydroxylysine metabolism

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.-5-2557C>T		intron_variant	Intron 1 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.-5-2557C>T		intron_variant	Intron 1 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.-5-2557C>T		intron_variant	Intron 1 of 4	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000566332.5	c.-5-2557C>T		intron_variant	Intron 1 of 3	1		ENSP00000457154.1
HYKK	ENST00000408962.6	c.-5-2557C>T		intron_variant	Intron 1 of 4	5		ENSP00000386197.2
HYKK	ENST00000566289.5	n.-5-2557C>T		intron_variant	Intron 1 of 4	2		ENSP00000456614.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99210 AN: 151746 Hom.: 32526 Cov.: 30

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.654 AC: 99281 AN: 151864 Hom.: 32554 Cov.: 30 AF XY: 0.659 AC XY: 48914 AN XY: 74216

African (AFR) AF: 0.632 AC: 26151 AN: 41358

American (AMR) AF: 0.741 AC: 11309 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2194 AN: 3468

East Asian (EAS) AF: 0.687 AC: 3544 AN: 5162

South Asian (SAS) AF: 0.740 AC: 3572 AN: 4826

European-Finnish (FIN) AF: 0.652 AC: 6871 AN: 10542

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43565 AN: 67926

Other (OTH) AF: 0.655 AC: 1382 AN: 2110

Alfa AF: 0.656 Hom.: 65230

Bravo AF: 0.658

Asia WGS AF: 0.725 AC: 2519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9788721; hg19: chr15-78802869;