Variant 15-74837243-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099436.4(ULK3):c.1404T>G(p.Ser468=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,583,116 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 12 hom., cov: 32)

Exomes 𝑓: 0.014 ( 192 hom. )

Consequence

ULK3
NM_001099436.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0006223

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0150

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 15-74837243-A-C is Benign according to our data. Variant chr15-74837243-A-C is described in ClinVar as [Benign]. Clinvar id is 787681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0135 (19354/1431032) while in subpopulation NFE AF= 0.0167 (18285/1095074). AF 95% confidence interval is 0.0165. There are 192 homozygotes in gnomad4_exome. There are 9342 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK3	NM_001099436.4 linkuse as main transcript	c.1404T>G	p.Ser468=	splice_region_variant, synonymous_variant	16/16	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.1404T>G	p.Ser468=	splice_region_variant, synonymous_variant	16/16	2	NM_001099436.4	ENSP00000400312	A1	Q6PHR2-1

Frequencies

GnomAD3 genomes

AF:

0.00855

AC:

1300

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0158

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00742

AC:

1664

AN:

224118

Hom.:

AF XY:

0.00773

AC XY:

929

AN XY:

120148

show subpopulations

Gnomad AFR exome

AF:

0.00196

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.000810

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000406

Gnomad FIN exome

AF:

0.00138

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.00813

GnomAD4 exome

AF:

0.0135

AC:

19354

AN:

1431032

Hom.:

192

Cov.:

AF XY:

0.0132

AC XY:

9342

AN XY:

708048

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00365

Gnomad4 ASJ exome

AF:

0.00144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000745

Gnomad4 FIN exome

AF:

0.00196

Gnomad4 NFE exome

AF:

0.0167

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.00854

AC:

1299

AN:

152084

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

563

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0158

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.00882

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.44

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00062

dbscSNV1_RF

Benign

0.086

SpliceAI score (max)

0.040

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