Genetic Variant NM_001099436.4: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.

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	Effect	Exon Rank	Protein	UniProt
ULK3	NM_001099436.4	MANE Select	c.1403-9C>T	intron	N/A	NP_001092906.3	Q6PHR2-1
ULK3	NM_001411082.1		c.1436-9C>T	intron	N/A	NP_001398011.1	Q6PHR2-4
ULK3	NM_001284364.3		c.1397-9C>T	intron	N/A	NP_001271293.2	Q6PHR2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ULK3	ENST00000440863.7	TSL:2 MANE Select	c.1403-9C>T	intron	N/A	ENSP00000400312.2	Q6PHR2-1
ULK3	ENST00000569437.5	TSL:1	c.1397-9C>T	intron	N/A	ENSP00000456051.1	Q6PHR2-3
ULK3	ENST00000566479.5	TSL:1	n.1589-9C>T	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over