rs8031948

Variant names:

• chr15-78523715-G-T
• rs8031948
• NM_001013619.4:c.478-3665G>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.478-3665G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,106 control chromosomes in the GnomAD database, including 6,373 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 0.27 (6373 hom., cov: 32)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 40 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	NM_001013619.4	MANE Select	c.478-3665G>T		intron	N/A	NP_001013641.2
	HYKK	NM_001083612.2		c.478-3665G>T		intron	N/A	NP_001077081.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	ENST00000388988.9	TSL:5 MANE Select	c.478-3665G>T		intron	N/A	ENSP00000373640.4
	HYKK	ENST00000566332.5	TSL:1	c.478-3665G>T		intron	N/A	ENSP00000457154.1
	HYKK	ENST00000569878.5	TSL:5	c.478-3665G>T		intron	N/A	ENSP00000455459.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41287 AN: 151988 Hom.: 6373 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.272 AC: 41304 AN: 152106 Hom.: 6373 Cov.: 32 AF XY: 0.268 AC XY: 19933 AN XY: 74346

African (AFR) AF: 0.163 AC: 6774 AN: 41500

American (AMR) AF: 0.232 AC: 3551 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3472

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5176

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4816

European-Finnish (FIN) AF: 0.333 AC: 3514 AN: 10564

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23868 AN: 67982

Other (OTH) AF: 0.287 AC: 606 AN: 2112

Alfa AF: 0.301 Hom.: 926

Bravo AF: 0.258

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.59
PhyloP100		0.36
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: rs8031948; hg19: chr15-78816057;