chr15-78527424-C-G

Position:

• chr15-78527424-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013619.4(HYKK):​c.522C>G​(p.Phe174Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HYKK NM_001013619.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.522C>G	p.Phe174Leu	missense_variant	4/5	ENST00000388988.9
HYKK	NM_001083612.2	c.522C>G	p.Phe174Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.522C>G	p.Phe174Leu	missense_variant	4/5	5	NM_001013619.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.522C>G (p.F174L) alteration is located in exon 4 (coding exon 3) of the HYKK gene. This alteration results from a C to G substitution at nucleotide position 522, causing the phenylalanine (F) at amino acid position 174 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.00010	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;.;T;T;.
Eigen	Benign	0.046
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.83	T;D;D;.;.
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;.;M;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N;N;N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.019	D;D;D;D;D
Sift4G	Benign	0.22	T;D;D;T;D
Polyphen		0.44	B;P;.;B;P
Vest4		0.74
MutPred		0.55		Gain of catalytic residue at F174 (P = 0.0199);Gain of catalytic residue at F174 (P = 0.0199);Gain of catalytic residue at F174 (P = 0.0199);Gain of catalytic residue at F174 (P = 0.0199);Gain of catalytic residue at F174 (P = 0.0199);
MVP		0.38
MPC		0.68
ClinPred		0.93	D
GERP RS		3.9
Varity_R		0.33
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-78819766;