rs8034191

Variant names:

• chr15-78513681-T-C
• rs8034191
• NM_001013619.4:c.337+256T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5 BP4 BA1

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
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.649
• Publications: 262 publications found

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

ACMG classification

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	c.337+256T>C		intron_variant	Intron 2 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.337+256T>C		intron_variant	Intron 2 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.337+256T>C		intron_variant	Intron 2 of 4	5	NM_001013619.4	ENSP00000373640.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41387 AN: 152038 Hom.: 6409 Cov.: 32

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.: 32 AF XY: 0.269 AC XY: 19987 AN XY: 74402

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

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

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
DANN	Benign	0.35
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8034191; hg19: chr15-78806023;