15-78513447-G-C

Variant names:

• chr15-78513447-G-C
• rs16969922
• NM_001013619.4:c.337+22G>C

Variant summary

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

The NM_001013619.4(HYKK):​c.337+22G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 1,537,800 control chromosomes in the GnomAD database, including 865 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 0.042 (457 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (408 hom.)
• Consequence: HYKK NM_001013619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.337+22G>C		intron_variant	Intron 2 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.337+22G>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+22G>C		intron_variant	Intron 2 of 4	5	NM_001013619.4	ENSP00000373640.4

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6398 AN: 152076 Hom.: 457 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.0121 AC: 2750 AN: 226522 Hom.: 183 AF XY: 0.00967 AC XY: 1190 AN XY: 123032

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.00723

Gnomad ASJ exome AF: 0.0180

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000456

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000488

Gnomad OTH exome AF: 0.00366

GnomAD4 exome AF: 0.00474 AC: 6569 AN: 1385604 Hom.: 408 Cov.: 23 AF XY: 0.00412 AC XY: 2848 AN XY: 691430

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.0192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000379

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.000263

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0421 AC: 6405 AN: 152196 Hom.: 457 Cov.: 31 AF XY: 0.0415 AC XY: 3085 AN XY: 74416

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.00564 Hom.: 9

Bravo AF: 0.0479

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.022
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs16969922; hg19: chr15-78805789;