rs3088051

Variant names:

• chr12-131922463-T-C
• rs3088051
• NM_003565.4:c.*1102T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK1	NM_003565.4	MANE Select	c.*1102T>C		3_prime_UTR	Exon 28 of 28	NP_003556.2	O75385

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK1	ENST00000321867.6	TSL:1 MANE Select	c.*1102T>C		3_prime_UTR	Exon 28 of 28	ENSP00000324560.3	O75385
	ULK1	ENST00000939866.1		c.*1102T>C		3_prime_UTR	Exon 28 of 28	ENSP00000609925.1
	ULK1	ENST00000939867.1		c.*1102T>C		3_prime_UTR	Exon 28 of 28	ENSP00000609926.1

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

African (AFR) AF: 0.123 AC: 59 AN: 480

American (AMR) AF: 0.211 AC: 394 AN: 1868

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 136 AN: 576

East Asian (EAS) AF: 0.0274 AC: 25 AN: 914

South Asian (SAS) AF: 0.322 AC: 1444 AN: 4488

European-Finnish (FIN) AF: 0.218 AC: 240 AN: 1102

Middle Eastern (MID) AF: 0.255 AC: 25 AN: 98

European-Non Finnish (NFE) AF: 0.259 AC: 3853 AN: 14852

Other (OTH) AF: 0.267 AC: 306 AN: 1146

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

African (AFR) AF: 0.145 AC: 6048 AN: 41586

American (AMR) AF: 0.259 AC: 3965 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3472

East Asian (EAS) AF: 0.0393 AC: 204 AN: 5188

South Asian (SAS) AF: 0.358 AC: 1727 AN: 4830

European-Finnish (FIN) AF: 0.240 AC: 2549 AN: 10618

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19593 AN: 67998

Other (OTH) AF: 0.285 AC: 601 AN: 2112

Alfa AF: 0.266 Hom.: 4286

Bravo AF: 0.228

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3088051;

hg19: chr12-132407008;