dbSNP rs28675338: HYKK:c.*1619C>T (chr15-78535289-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013619.4(HYKK):c.*1619C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000038 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HYKK
NM_001013619.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.606

Publications

7 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	NM_001013619.4	MANE Select	c.*1619C>T		3_prime_UTR	Exon 5 of 5	NP_001013641.2
	HYKK	NM_001083612.2		c.662-2011C>T		intron	N/A	NP_001077081.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HYKK	ENST00000388988.9	TSL:5 MANE Select	c.*1619C>T	3_prime_UTR	Exon 5 of 5	ENSP00000373640.4
HYKK	ENST00000569878.5	TSL:5	c.*1619C>T	3_prime_UTR	Exon 4 of 4	ENSP00000455459.1
HYKK	ENST00000408962.6	TSL:5	c.662-2011C>T	intron	N/A	ENSP00000386197.2

Frequencies

GnomAD3 genomes

AF:

0.0000306

AC:

AN:

130892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000216

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000316

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000382

AC:

AN:

130898

Hom.:

Cov.:

AF XY:

0.0000161

AC XY:

AN XY:

61960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000285

AC:

AN:

35040

American (AMR)

AF:

0.00

AC:

AN:

11876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.000217

AC:

AN:

4602

South Asian (SAS)

AF:

0.00

AC:

AN:

4088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.0000474

AC:

AN:

63344

Other (OTH)

AF:

0.00

AC:

AN:

1794

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.6

(source)

DANN

Benign

0.29

PhyloP100

0.61

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over