Genetic Variant HYKK:c.337+256T>C (chr15-78513681-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5BP4BA1

The NM_001013619.4(HYKK):c.337+256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,156 control chromosomes in the GnomAD database, including 6,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.27 ( 6412 hom., cov: 32)

Consequence

HYKK
NM_001013619.4 intron

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.649

Publications

262 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 -8 ACMG points.

PP5

Variant 15-78513681-T-C is Pathogenic according to our data. Variant chr15-78513681-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3336640.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89). . Strength limited to SUPPORTING due to the PP5.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4 link	c.337+256T>C		intron_variant	Intron 2 of 4	ENST00000388988.9	NP_001013641.2	A2RU49-1
HYKK	NM_001083612.2 link	c.337+256T>C		intron_variant	Intron 2 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.337+256T>C		intron_variant	Intron 2 of 4	5	NM_001013619.4	ENSP00000373640.4		A2RU49-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41387

AN:

152038

Hom.:

6409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.0286

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.272

AC:

41417

AN:

152156

Hom.:

6412

Cov.:

AF XY:

0.269

AC XY:

19987

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.166

AC:

6912

AN:

41530

American (AMR)

AF:

0.232

AC:

3550

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1199

AN:

3472

East Asian (EAS)

AF:

0.0289

AC:

150

AN:

5190

South Asian (SAS)

AF:

0.235

AC:

1135

AN:

4824

European-Finnish (FIN)

AF:

0.332

AC:

3514

AN:

10580

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.351

AC:

23858

AN:

67966

Other (OTH)

AF:

0.287

AC:

606

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1491

2983

4474

5966

7457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.316

Hom.:

38259

Bravo

AF:

0.260

Asia WGS

AF:

0.138

AC:

482

AN:

3478

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Chronic obstructive pulmonary disease

Pathogenic:1

Dr Mariam's Lab, University of the Punjab

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.9

(source)

DANN

Benign

0.35

PhyloP100

0.65

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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chr15-78513681-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over