rs8034191

Positions:

• chr15-78513681-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.337+256T>C		intron_variant		ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.337+256T>C		intron_variant			NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.337+256T>C		intron_variant		5	NM_001013619.4	ENSP00000373640	P1

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.0289

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.287

Alfa AF: 0.328 Hom.: 19811

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

Likely pathogenic, no assertion criteria provided

case-control

Dr Mariam's Lab, University of the Punjab

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs8034191; hg19: chr15-78806023; COSMIC: COSV64762226;