15-78533220-C-T

Variant names:

• chr15-78533220-C-T
• rs12906951
• NM_001013619.4:c.672C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001013619.4(HYKK):​c.672C>T​(p.His224His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,585,222 control chromosomes in the GnomAD database, including 125,584 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 0.32 (8582 hom., cov: 33)
  • Exomes 𝑓: 0.39 (117002 hom.)
• Consequence: HYKK NM_001013619.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 26 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.484 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4	c.672C>T	p.His224His	synonymous_variant	Exon 5 of 5	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2	c.662-4080C>T		intron_variant	Intron 4 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9	c.672C>T	p.His224His	synonymous_variant	Exon 5 of 5	5	NM_001013619.4	ENSP00000373640.4
HYKK	ENST00000569878.5	c.672C>T	p.His224His	synonymous_variant	Exon 4 of 4	5		ENSP00000455459.1
HYKK	ENST00000408962.6	c.662-4080C>T		intron_variant	Intron 4 of 4	5		ENSP00000386197.2
HYKK	ENST00000563233.2	c.662-4080C>T		intron_variant	Intron 3 of 3	2		ENSP00000454850.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47947 AN: 151958 Hom.: 8585 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.317

GnomAD2 exomes AF: 0.332 AC: 81247 AN: 244982 AF XY: 0.339

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.166

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.394 AC: 565132 AN: 1433146 Hom.: 117002 Cov.: 28 AF XY: 0.394 AC XY: 281609 AN XY: 714382

African (AFR) AF: 0.152 AC: 5004 AN: 32892

American (AMR) AF: 0.204 AC: 8934 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8941 AN: 25760

East Asian (EAS) AF: 0.124 AC: 4920 AN: 39596

South Asian (SAS) AF: 0.336 AC: 28496 AN: 84792

European-Finnish (FIN) AF: 0.365 AC: 19474 AN: 53302

Middle Eastern (MID) AF: 0.275 AC: 1567 AN: 5696

European-Non Finnish (NFE) AF: 0.428 AC: 465836 AN: 1087936

Other (OTH) AF: 0.370 AC: 21960 AN: 59398

GnomAD4 genome AF: 0.315 AC: 47956 AN: 152076 Hom.: 8582 Cov.: 33 AF XY: 0.313 AC XY: 23236 AN XY: 74328

African (AFR) AF: 0.163 AC: 6746 AN: 41472

American (AMR) AF: 0.250 AC: 3818 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3468

East Asian (EAS) AF: 0.165 AC: 853 AN: 5180

South Asian (SAS) AF: 0.344 AC: 1659 AN: 4816

European-Finnish (FIN) AF: 0.370 AC: 3913 AN: 10562

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28613 AN: 67966

Other (OTH) AF: 0.318 AC: 671 AN: 2112

Alfa AF: 0.371 Hom.: 16201

Bravo AF: 0.300

Asia WGS AF: 0.274 AC: 951 AN: 3478

EpiCase AF: 0.399

EpiControl AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.89
DANN	Benign	0.51
PhyloP100		-0.48
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12906951; hg19: chr15-78825562; COSMIC: COSV66459756; COSMIC: COSV66459756;