Variant rs3885951 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001013619.4(HYKK):c.1027A>G(p.Lys343Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,614,076 control chromosomes in the GnomAD database, including 6,575 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.070 ( 507 hom., cov: 33)

Exomes 𝑓: 0.087 ( 6068 hom. )

Consequence

HYKK
NM_001013619.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014449358).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4 linkuse as main transcript	c.1027A>G	p.Lys343Glu	missense_variant	5/5	ENST00000388988.9
HYKK	NM_001083612.2 linkuse as main transcript	c.662-3725A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9 linkuse as main transcript	c.1027A>G	p.Lys343Glu	missense_variant	5/5	5	NM_001013619.4	P1	A2RU49-1
HYKK	ENST00000569878.5 linkuse as main transcript	c.1027A>G	p.Lys343Glu	missense_variant	4/4	5		P1	A2RU49-1
HYKK	ENST00000408962.6 linkuse as main transcript	c.662-3725A>G		intron_variant		5			A2RU49-3
HYKK	ENST00000563233.2 linkuse as main transcript	c.662-3725A>G		intron_variant		2			A2RU49-3

Frequencies

GnomAD3 genomes

AF:

0.0696

AC:

10593

AN:

152166

Hom.:

508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0891

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0567

Gnomad FIN

AF:

0.0562

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.0932

GnomAD3 exomes

AF:

0.0753

AC:

18779

AN:

249552

Hom.:

927

AF XY:

0.0786

AC XY:

10646

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.0145

Gnomad AMR exome

AF:

0.0608

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0609

Gnomad FIN exome

AF:

0.0576

Gnomad NFE exome

AF:

0.0993

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0871

AC:

127353

AN:

1461792

Hom.:

6068

Cov.:

AF XY:

0.0868

AC XY:

63101

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.0646

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0615

Gnomad4 FIN exome

AF:

0.0616

Gnomad4 NFE exome

AF:

0.0949

Gnomad4 OTH exome

AF:

0.0866

GnomAD4 genome

AF:

0.0696

AC:

10592

AN:

152284

Hom.:

507

Cov.:

AF XY:

0.0673

AC XY:

5009

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.0890

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0567

Gnomad4 FIN

AF:

0.0562

Gnomad4 NFE

AF:

0.0992

Gnomad4 OTH

AF:

0.0922

Alfa

AF:

0.0951

Hom.:

1990

Bravo

AF:

0.0701

TwinsUK

AF:

0.101

AC:

376

ALSPAC

AF:

0.0963

AC:

371

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.104

AC:

855

ExAC

AF:

0.0752

AC:

9090

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.051

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

T;.

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.0064

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.068

Sift

Benign

0.15

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0060

B;B

Vest4

0.092

MPC

0.21

ClinPred

0.026

GERP RS

5.8

Varity_R

0.28

gMVP

0.19

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

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