15-78515039-C-T

Variant names:

• chr15-78515039-C-T
• rs762296061
• NM_001013619.4:c.409C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013619.4(HYKK):​c.409C>T​(p.Leu137Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L137I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HYKK NM_001013619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04944408).

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.409C>T	p.Leu137Phe	missense	Exon 3 of 5	NP_001013641.2	A2RU49-1
	HYKK	NM_001083612.2		c.409C>T	p.Leu137Phe	missense	Exon 3 of 5	NP_001077081.1	A2RU49-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	ENST00000388988.9	TSL:5 MANE Select	c.409C>T	p.Leu137Phe	missense	Exon 3 of 5	ENSP00000373640.4	A2RU49-1
	HYKK	ENST00000566332.5	TSL:1	c.409C>T	p.Leu137Phe	missense	Exon 3 of 4	ENSP00000457154.1	A0A0C4DGM4
	HYKK	ENST00000569878.5	TSL:5	c.409C>T	p.Leu137Phe	missense	Exon 2 of 4	ENSP00000455459.1	A2RU49-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.016
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.065
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.27	B
Vest4		0.068
MutPred		0.41		Gain of helix (P = 0.2294)
MVP		0.030
MPC		0.23
ClinPred		0.22	T
GERP RS		-11
Varity_R		0.11
gMVP		0.63
Mutation Taster		=80/20	polymorphism

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: rs762296061; hg19: chr15-78807381;