Variant rs12906951 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001013619.4(HYKK):c.672C>A(p.His224Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,590,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

HYKK
NM_001013619.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.484

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYKK	NM_001013619.4 linkuse as main transcript	c.672C>A	p.His224Gln	missense_variant	5/5	ENST00000388988.9	NP_001013641.2	A2RU49-1
HYKK	NM_001083612.2 linkuse as main transcript	c.662-4080C>A		intron_variant			NP_001077081.1	A2RU49-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HYKK	ENST00000388988.9 linkuse as main transcript	c.672C>A	p.His224Gln	missense_variant	5/5	5	NM_001013619.4	ENSP00000373640.4	A2RU49-1
HYKK	ENST00000569878.5 linkuse as main transcript	c.672C>A	p.His224Gln	missense_variant	4/4	5		ENSP00000455459.1	A2RU49-1
HYKK	ENST00000408962.6 linkuse as main transcript	c.662-4080C>A		intron_variant		5		ENSP00000386197.2	A2RU49-3
HYKK	ENST00000563233.2 linkuse as main transcript	c.662-4080C>A		intron_variant		2		ENSP00000454850.1	A2RU49-3

Frequencies

GnomAD3 genomes

AF:

0.000461

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

244982

Hom.:

AF XY:

0.0000979

AC XY:

AN XY:

132800

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000507

AC:

AN:

1438472

Hom.:

Cov.:

AF XY:

0.0000335

AC XY:

AN XY:

716760

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000460

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000132

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.86

D;.

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

0.45

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.2

D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.98

MutPred

0.90

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.57

MPC

0.65

ClinPred

0.24

GERP RS

-3.9

Varity_R

0.82

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over