dbSNP rs16969922: HYKK:c.337+22G>A (chr15-78513447-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013619.4(HYKK):c.337+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,537,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HYKK
NM_001013619.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	NM_001013619.4	MANE Select	c.337+22G>A		intron	N/A	NP_001013641.2	A2RU49-1
	HYKK	NM_001083612.2		c.337+22G>A		intron	N/A	NP_001077081.1	A2RU49-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYKK	ENST00000388988.9	TSL:5 MANE Select	c.337+22G>A	intron	N/A	ENSP00000373640.4	A2RU49-1
HYKK	ENST00000566332.5	TSL:1	c.337+22G>A	intron	N/A	ENSP00000457154.1	A0A0C4DGM4
HYKK	ENST00000569878.5	TSL:5	c.337+22G>A	intron	N/A	ENSP00000455459.1	A2RU49-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.00000441

AC:

AN:

226522

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000956

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1385622

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

691438

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31778

American (AMR)

AF:

0.00

AC:

AN:

42378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24490

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39344

South Asian (SAS)

AF:

0.00

AC:

AN:

81822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1053236

Other (OTH)

AF:

0.00

AC:

AN:

57832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000444

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.037

(source)

DANN

Benign

0.59

PhyloP100

-1.3

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over