rs12441354

chr15-78528674-G-Achr15-78528674-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013619.4(HYKK):c.661+1111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 313,156 control chromosomes in the GnomAD database, including 10,360 homozygotes. 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 0.27 (6379 hom., cov: 31)
  • Exomes 𝑓: 0.21 (3981 hom.)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYKK	NM_001013619.4	c.661+1111G>A		intron_variant		ENST00000388988.9
HYKK	NM_001083612.2	c.661+1111G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYKK	ENST00000388988.9	c.661+1111G>A		intron_variant		5	NM_001013619.4	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41502 AN: 151668 Hom.: 6365 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.215 AC: 34694 AN: 161370 Hom.: 3981 Cov.: 5 AF XY: 0.215 AC XY: 16644 AN XY: 77266

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.274 AC: 41540 AN: 151786 Hom.: 6379 Cov.: 31 AF XY: 0.282 AC XY: 20894 AN XY: 74202

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.286

Alfa AF: 0.239 Hom.: 633

Bravo AF: 0.286

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.62
Dann	Benign	0.34

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: rs12441354; hg19: chr15-78821016;