Variant chr15-78533551-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013619.4(HYKK):c.1003A>C(p.Met335Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HYKK
NM_001013619.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.76

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14786467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYKK	NM_001013619.4 linkuse as main transcript	c.1003A>C	p.Met335Leu	missense_variant	5/5	ENST00000388988.9	NP_001013641.2
HYKK	NM_001083612.2 linkuse as main transcript	c.662-3749A>C		intron_variant			NP_001077081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYKK	ENST00000388988.9 linkuse as main transcript	c.1003A>C	p.Met335Leu	missense_variant	5/5	5	NM_001013619.4	ENSP00000373640	P1	A2RU49-1
HYKK	ENST00000569878.5 linkuse as main transcript	c.1003A>C	p.Met335Leu	missense_variant	4/4	5		ENSP00000455459	P1	A2RU49-1
HYKK	ENST00000408962.6 linkuse as main transcript	c.662-3749A>C		intron_variant		5		ENSP00000386197		A2RU49-3
HYKK	ENST00000563233.2 linkuse as main transcript	c.662-3749A>C		intron_variant		2		ENSP00000454850		A2RU49-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000507

AC:

AN:

1459990

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.1003A>C (p.M335L) alteration is located in exon 5 (coding exon 4) of the HYKK gene. This alteration results from a A to C substitution at nucleotide position 1003, causing the methionine (M) at amino acid position 335 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0040

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.044

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

0.36

N;N

REVEL

Benign

0.11

Sift

Benign

0.67

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0010

B;B

Vest4

0.22

MutPred

0.59

Gain of ubiquitination at K331 (P = 0.0737);Gain of ubiquitination at K331 (P = 0.0737);

MVP

0.14

MPC

0.14

ClinPred

0.76

GERP RS

5.8

Varity_R

0.27

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over