Genetic Variant NM_001013619.4:c.477+3496G>A (chr15-78518603-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001013619.4(HYKK):c.477+3496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 455,482 control chromosomes in the GnomAD database, including 364 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 0.034 ( 293 hom., cov: 31)

Exomes 𝑓: 0.0052 ( 71 hom. )

Consequence

HYKK
NM_001013619.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

2 publications found

Variant links:

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

HYKK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.121).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYKK	NM_001013619.4 link	c.477+3496G>A		intron_variant	Intron 3 of 4	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2 link	c.477+3496G>A		intron_variant	Intron 3 of 4		NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9 link	c.477+3496G>A		intron_variant	Intron 3 of 4	5	NM_001013619.4	ENSP00000373640.4

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

5155

AN:

151992

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0235

GnomAD2 exomes

AF:

0.00849

AC:

1139

AN:

134236

AF XY:

0.00706

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.00620

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.0000954

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000645

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.00518

AC:

1572

AN:

303372

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

696

AN XY:

172846

show subpopulations

African (AFR)

AF:

0.117

AC:

1000

AN:

8572

American (AMR)

AF:

0.00635

AC:

173

AN:

27260

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

210

AN:

10784

East Asian (EAS)

AF:

0.000109

AC:

AN:

9168

South Asian (SAS)

AF:

0.000352

AC:

AN:

59668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12788

Middle Eastern (MID)

AF:

0.00418

AC:

AN:

2152

European-Non Finnish (NFE)

AF:

0.000321

AC:

AN:

158826

Other (OTH)

AF:

0.00756

AC:

107

AN:

14154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

126

188

251

314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0339

AC:

5161

AN:

152110

Hom.:

293

Cov.:

AF XY:

0.0334

AC XY:

2482

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.116

AC:

4825

AN:

41484

American (AMR)

AF:

0.0124

AC:

189

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68000

Other (OTH)

AF:

0.0232

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

219

439

658

878

1097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0112

Hom.:

102

Bravo

AF:

0.0381

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.30

(source)

DANN

Benign

0.20

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over