dbSNP rs2290573: ULK3:c.1403-9C>T (chr15-74837253-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001099436.4(ULK3):c.1403-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,592,098 control chromosomes in the GnomAD database, including 197,973 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 0.36 ( 12702 hom., cov: 31)

Exomes 𝑓: 0.49 ( 185271 hom. )

Consequence

ULK3
NM_001099436.4 intron

Scores

Splicing: ADA: 0.0007426

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.535

Publications

25 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK3	NM_001099436.4 link	c.1403-9C>T		intron_variant	Intron 15 of 15	ENST00000440863.7	NP_001092906.3	Q6PHR2-1B4DDG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK3	ENST00000440863.7 link	c.1403-9C>T		intron_variant	Intron 15 of 15	2	NM_001099436.4	ENSP00000400312.2		Q6PHR2-1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54895

AN:

151860

Hom.:

12703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0968

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.388

AC:

89824

AN:

231608

AF XY:

0.385

show subpopulations

Gnomad AFR exome

AF:

0.0865

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.489

AC:

703604

AN:

1440120

Hom.:

185271

Cov.:

AF XY:

0.479

AC XY:

341643

AN XY:

713688

show subpopulations

African (AFR)

AF:

0.0826

AC:

2745

AN:

33232

American (AMR)

AF:

0.359

AC:

15625

AN:

43556

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

10239

AN:

24346

East Asian (EAS)

AF:

0.177

AC:

7007

AN:

39514

South Asian (SAS)

AF:

0.145

AC:

11917

AN:

82360

European-Finnish (FIN)

AF:

0.463

AC:

24223

AN:

52350

Middle Eastern (MID)

AF:

0.331

AC:

1877

AN:

5666

European-Non Finnish (NFE)

AF:

0.549

AC:

603660

AN:

1099560

Other (OTH)

AF:

0.442

AC:

26311

AN:

59536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

18587

37174

55762

74349

92936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16778

33556

50334

67112

83890

<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:

0.361

AC:

54896

AN:

151978

Hom.:

12702

Cov.:

AF XY:

0.352

AC XY:

26148

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0965

AC:

4002

AN:

41462

American (AMR)

AF:

0.404

AC:

6168

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

1433

AN:

3468

East Asian (EAS)

AF:

0.166

AC:

857

AN:

5160

South Asian (SAS)

AF:

0.138

AC:

662

AN:

4812

European-Finnish (FIN)

AF:

0.461

AC:

4860

AN:

10548

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.526

AC:

35745

AN:

67936

Other (OTH)

AF:

0.363

AC:

766

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1552

3103

4655

6206

7758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.454

Hom.:

23850

Bravo

AF:

0.352

Asia WGS

AF:

0.140

AC:

490

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.7

(source)

DANN

Benign

0.31

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00074

dbscSNV1_RF

Benign

0.014

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