Variant 15-74838187-G-A 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_001099436.4(ULK3):c.1252C>T(p.Pro418Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,413,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ULK3
NM_001099436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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:

ULK3 (HGNC:):

ULK3 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=0.23092976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK3	NM_001099436.4 linkuse as main transcript	c.1252C>T	p.Pro418Ser	missense_variant	13/16	ENST00000440863.7	NP_001092906.3	Q6PHR2-1B4DDG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK3	ENST00000440863.7 linkuse as main transcript	c.1252C>T	p.Pro418Ser	missense_variant	13/16	2	NM_001099436.4	ENSP00000400312.2		Q6PHR2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000571

AC:

AN:

174980

Hom.:

AF XY:

0.00

AC XY:

AN XY:

93896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000793

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1413588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000850

AC:

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, 2023

The c.1252C>T (p.P418S) alteration is located in exon 13 (coding exon 13) of the ULK3 gene. This alteration results from a C to T substitution at nucleotide position 1252, causing the proline (P) at amino acid position 418 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.059

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

T;T;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.078

Sift

Benign

0.089

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.35

MutPred

0.48

.;.;Loss of catalytic residue at P429 (P = 0.0077);

MVP

0.57

MPC

0.28

ClinPred

0.36

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.11

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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