15-74837253-G-A

Variant names:

• chr15-74837253-G-A
• rs2290573
• NM_001099436.4:c.1403-9C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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

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

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

Ensembl Transcripts

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

GnomAD2 exomes AF: 0.388 AC: 89824 AN: 231608 AF XY: 0.385

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

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

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

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

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
DANN	Benign	0.31
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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