Variant 15-74838721-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001099436.4(ULK3):c.1024G>A(p.Glu342Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000617 in 1,458,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ULK3
NM_001099436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

ULK3 (HGNC:19703): (unc-51 like kinase 3) Enables protein serine/threonine kinase activity. Involved in several processes, including fibroblast activation; protein autophosphorylation; and regulation of smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ULK3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.92

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK3	NM_001099436.4 linkuse as main transcript	c.1024G>A	p.Glu342Lys	missense_variant	10/16	ENST00000440863.7	NP_001092906.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK3	ENST00000440863.7 linkuse as main transcript	c.1024G>A	p.Glu342Lys	missense_variant	10/16	2	NM_001099436.4	ENSP00000400312	A1	Q6PHR2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242914

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1458868

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000469

Hom.:

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

Sep 12, 2023

The c.1024G>A (p.E342K) alteration is located in exon 10 (coding exon 10) of the ULK3 gene. This alteration results from a G to A substitution at nucleotide position 1024, causing the glutamic acid (E) at amino acid position 342 to be replaced by a lysine (K). 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

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;.;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.5

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D;T

Sift4G

Benign

0.062

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.76

MutPred

0.78

.;.;Gain of MoRF binding (P = 0.002);

MVP

0.77

MPC

1.0

ClinPred

0.96

GERP RS

5.0

Varity_R

0.56

gMVP

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over