chr15-78528674-G-A

Variant names:

• chr15-78528674-G-A
• rs12441354
• NM_001013619.4:c.661+1111G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	NM_001013619.4	MANE Select	c.661+1111G>A		intron	N/A	NP_001013641.2
	HYKK	NM_001083612.2		c.661+1111G>A		intron	N/A	NP_001077081.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYKK	ENST00000388988.9	TSL:5 MANE Select	c.661+1111G>A		intron	N/A	ENSP00000373640.4
	HYKK	ENST00000566289.5	TSL:2	n.*1439G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000456614.1
	HYKK	ENST00000566289.5	TSL:2	n.*1439G>A		3_prime_UTR	Exon 5 of 5	ENSP00000456614.1

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

African (AFR) AF: 0.258 AC: 738 AN: 2866

American (AMR) AF: 0.546 AC: 95 AN: 174

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 214 AN: 992

East Asian (EAS) AF: 0.393 AC: 245 AN: 624

South Asian (SAS) AF: 0.369 AC: 1121 AN: 3034

European-Finnish (FIN) AF: 0.321 AC: 18 AN: 56

Middle Eastern (MID) AF: 0.293 AC: 95 AN: 324

European-Non Finnish (NFE) AF: 0.209 AC: 30881 AN: 148106

Other (OTH) AF: 0.248 AC: 1287 AN: 5194

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

African (AFR) AF: 0.269 AC: 11118 AN: 41354

American (AMR) AF: 0.469 AC: 7153 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2055 AN: 5152

South Asian (SAS) AF: 0.385 AC: 1850 AN: 4802

European-Finnish (FIN) AF: 0.281 AC: 2961 AN: 10520

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14764 AN: 67932

Other (OTH) AF: 0.286 AC: 604 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.34
PhyloP100		0.36
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: rs12441354; hg19: chr15-78821016;