rs3088051

Positions:

• chr12-131922463-T-C

Variant summary

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

The NM_003565.4(ULK1):​c.*1102T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 177,832 control chromosomes in the GnomAD database, including 5,597 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 0.24 (4663 hom., cov: 34)
  • Exomes 𝑓: 0.25 (934 hom.)
• Consequence: ULK1 NM_003565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

Genes affected

ULK1 (HGNC:12558): (unc-51 like autophagy activating kinase 1) Enables identical protein binding activity; protein serine/threonine kinase activity; and small GTPase binding activity. Involved in several processes, including autophagosome assembly; positive regulation by symbiont of host autophagy; and protein phosphorylation. Located in autophagosome; cytosol; and phagophore assembly site membrane. Is extrinsic component of autophagosome membrane; extrinsic component of omegasome membrane; and extrinsic component of phagophore assembly site membrane. Part of Atg1/ULK1 kinase complex. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK1	NM_003565.4	c.*1102T>C		3_prime_UTR_variant	28/28	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.*1102T>C		3_prime_UTR_variant	28/28		XP_011537100.1
ULK1	XM_011538799.3	c.*1102T>C		3_prime_UTR_variant	28/28		XP_011537101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.*1102T>C		3_prime_UTR_variant	28/28	1	NM_003565.4	ENSP00000324560.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35906 AN: 152190 Hom.: 4660 Cov.: 34

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.254 AC: 6482 AN: 25524 Hom.: 934 Cov.: 0 AF XY: 0.261 AC XY: 3654 AN XY: 14002

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.0274

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.236 AC: 35912 AN: 152308 Hom.: 4663 Cov.: 34 AF XY: 0.234 AC XY: 17442 AN XY: 74460

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0393

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.285

Alfa AF: 0.263 Hom.: 2410

Bravo AF: 0.228

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs3088051; hg19: chr12-132407008;