Genetic Variant HYKK:c.*936T>C (chr15-78534606-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001013619.4(HYKK):c.*936T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,130 control chromosomes in the GnomAD database, including 5,936 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 0.26 ( 5936 hom., cov: 31)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

HYKK
NM_001013619.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.817

Publications

53 publications found

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 Gene-Disease associations (from GenCC):

inborn disorder of lysine and hydroxylysine metabolism
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

HYKK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4 link	c.*936T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2 link	c.662-2694T>C		intron_variant	Intron 4 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HYKK	ENST00000388988.9 link	c.*936T>C	3_prime_UTR_variant	Exon 5 of 5	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000569878.5 link	c.*936T>C	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000455459.1
HYKK	ENST00000408962.6 link	c.662-2694T>C	intron_variant	Intron 4 of 4	5		ENSP00000386197.2
HYKK	ENST00000563233.2 link	c.662-2694T>C	intron_variant	Intron 3 of 3	2		ENSP00000454850.1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39777

AN:

151996

Hom.:

5921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.262

AC:

39810

AN:

152114

Hom.:

5936

Cov.:

AF XY:

0.270

AC XY:

20097

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.224

AC:

9291

AN:

41512

American (AMR)

AF:

0.461

AC:

7033

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3470

East Asian (EAS)

AF:

0.444

AC:

2293

AN:

5162

South Asian (SAS)

AF:

0.387

AC:

1867

AN:

4824

European-Finnish (FIN)

AF:

0.280

AC:

2958

AN:

10572

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.217

AC:

14760

AN:

67996

Other (OTH)

AF:

0.277

AC:

583

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1434

2868

4303

5737

7171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.246

Hom.:

3741

Bravo

AF:

0.273

Asia WGS

AF:

0.404

AC:

1405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.8

(source)

DANN

Benign

0.76

PhyloP100

0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over