rs2290573

chr15-74837253-G-Achr15-74837253-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099436.4(ULK3):c.1403-9C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0007426
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ULK3	NM_001099436.4	c.1403-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000440863.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK3	ENST00000440863.7	c.1403-9C>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_001099436.4	A1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54895 AN: 151860 Hom.: 12703 Cov.: 31

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

GnomAD3 exomes AF: 0.388 AC: 89824 AN: 231608 Hom.: 20630 AF XY: 0.385 AC XY: 48045 AN XY: 124770

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 SAS exome AF: 0.136

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.: 53 AF XY: 0.479 AC XY: 341643 AN XY: 713688

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.361 AC: 54896 AN: 151978 Hom.: 12702 Cov.: 31 AF XY: 0.352 AC XY: 26148 AN XY: 74266

Gnomad4 AFR AF: 0.0965

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.363

Alfa AF: 0.356 Hom.: 2134

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
Dann	Benign	0.31

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

LitVar

Other links and lift over

dbSNP: rs2290573; hg19: chr15-75129594; COSMIC: COSV71348176; COSMIC: COSV71348176;