Genetic Variant ULK3:p.Arg423Gln (chr15-74838171-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001099436.4(ULK3):c.1268G>A(p.Arg423Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000295 in 1,561,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R423W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ULK3
NM_001099436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099436.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ULK3	NM_001099436.4	MANE Select	c.1268G>A	p.Arg423Gln	missense	Exon 13 of 16	NP_001092906.3	Q6PHR2-1
ULK3	NM_001411082.1		c.1301G>A	p.Arg434Gln	missense	Exon 13 of 16	NP_001398011.1	Q6PHR2-4
ULK3	NM_001284364.3		c.1268G>A	p.Arg423Gln	missense	Exon 13 of 16	NP_001271293.2	Q6PHR2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ULK3	ENST00000440863.7	TSL:2 MANE Select	c.1268G>A	p.Arg423Gln	missense	Exon 13 of 16	ENSP00000400312.2	Q6PHR2-1
ULK3	ENST00000569437.5	TSL:1	c.1268G>A	p.Arg423Gln	missense	Exon 13 of 16	ENSP00000456051.1	Q6PHR2-3
ULK3	ENST00000566479.5	TSL:1	n.1454G>A		splice_region non_coding_transcript_exon	Exon 12 of 15

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000117

AC:

AN:

170310

AF XY:

0.000110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000153

Gnomad ASJ exome

AF:

0.00115

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000429

Gnomad OTH exome

AF:

0.000646

GnomAD4 exome

AF:

0.0000298

AC:

AN:

1409080

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

696188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32042

American (AMR)

AF:

0.000108

AC:

AN:

37108

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

25308

East Asian (EAS)

AF:

0.00

AC:

AN:

36560

South Asian (SAS)

AF:

0.00

AC:

AN:

79836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50086

Middle Eastern (MID)

AF:

0.000453

AC:

AN:

4412

European-Non Finnish (NFE)

AF:

0.00000645

AC:

AN:

1085374

Other (OTH)

AF:

0.0000171

AC:

AN:

58354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.000196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000180

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000600

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.8

PhyloP100

5.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Uncertain

0.0090

Sift4G

Benign

0.092

Polyphen

1.0

Vest4

0.71

MVP

0.62

MPC

0.98

ClinPred

0.63

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.56

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over