dbSNP rs12441354: HYKK:c.661+1111G>A (chr15-78528674-G-A) – 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.661+1111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 313,156 control chromosomes in the GnomAD database, including 10,360 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 0.27 ( 6379 hom., cov: 31)

Exomes 𝑓: 0.21 ( 3981 hom. )

Consequence

HYKK
NM_001013619.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.365

Publications

10 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=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4 link	c.661+1111G>A		intron_variant	Intron 4 of 4	ENST00000388988.9	NP_001013641.2	A2RU49-1
HYKK	NM_001083612.2 link	c.661+1111G>A		intron_variant	Intron 4 of 4		NP_001077081.1	A2RU49-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9 link	c.661+1111G>A		intron_variant	Intron 4 of 4	5	NM_001013619.4	ENSP00000373640.4		A2RU49-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41502

AN:

151668

Hom.:

6365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.215

AC:

34694

AN:

161370

Hom.:

3981

Cov.:

AF XY:

0.215

AC XY:

16644

AN XY:

77266

show subpopulations

African (AFR)

AF:

0.258

AC:

738

AN:

2866

American (AMR)

AF:

0.546

AC:

AN:

174

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

214

AN:

992

East Asian (EAS)

AF:

0.393

AC:

245

AN:

624

South Asian (SAS)

AF:

0.369

AC:

1121

AN:

3034

European-Finnish (FIN)

AF:

0.321

AC:

AN:

Middle Eastern (MID)

AF:

0.293

AC:

AN:

324

European-Non Finnish (NFE)

AF:

0.209

AC:

30881

AN:

148106

Other (OTH)

AF:

0.248

AC:

1287

AN:

5194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1339

2677

4016

5354

6693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1484

2968

4452

5936

7420

<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:

0.274

AC:

41540

AN:

151786

Hom.:

6379

Cov.:

AF XY:

0.282

AC XY:

20894

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.269

AC:

11118

AN:

41354

American (AMR)

AF:

0.469

AC:

7153

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

796

AN:

3472

East Asian (EAS)

AF:

0.399

AC:

2055

AN:

5152

South Asian (SAS)

AF:

0.385

AC:

1850

AN:

4802

European-Finnish (FIN)

AF:

0.281

AC:

2961

AN:

10520

Middle Eastern (MID)

AF:

0.325

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.217

AC:

14764

AN:

67932

Other (OTH)

AF:

0.286

AC:

604

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1468

2937

4405

5874

7342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.239

Hom.:

633

Bravo

AF:

0.286

Asia WGS

AF:

0.398

AC:

1383

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.62

(source)

DANN

Benign

0.34

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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