12-131914520-T-G

Variant names:

• chr12-131914520-T-G
• rs12303764
• NM_003565.4:c.1373+43T>G

Variant summary

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

The NM_003565.4(ULK1):​c.1373+43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,588,298 control chromosomes in the GnomAD database, including 95,901 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 0.26 (6463 hom., cov: 35)
  • Exomes 𝑓: 0.35 (89438 hom.)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 36 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4	c.1373+43T>G		intron_variant	Intron 16 of 27	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.1373+43T>G		intron_variant	Intron 16 of 27		XP_011537100.1
ULK1	XM_011538799.3	c.1373+43T>G		intron_variant	Intron 16 of 27		XP_011537101.1
ULK1	XR_007063134.1	n.1753+43T>G		intron_variant	Intron 16 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.1373+43T>G		intron_variant	Intron 16 of 27	1	NM_003565.4	ENSP00000324560.3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39649 AN: 152034 Hom.: 6469 Cov.: 35

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.299 AC: 65701 AN: 219888 AF XY: 0.307

Gnomad AFR exome AF: 0.0583

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.328

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.347 AC: 498855 AN: 1436146 Hom.: 89438 Cov.: 34 AF XY: 0.347 AC XY: 246464 AN XY: 711240

African (AFR) AF: 0.0548 AC: 1806 AN: 32980

American (AMR) AF: 0.231 AC: 9824 AN: 42468

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 8335 AN: 25582

East Asian (EAS) AF: 0.226 AC: 8729 AN: 38622

South Asian (SAS) AF: 0.276 AC: 23395 AN: 84622

European-Finnish (FIN) AF: 0.327 AC: 16570 AN: 50614

Middle Eastern (MID) AF: 0.331 AC: 1826 AN: 5514

European-Non Finnish (NFE) AF: 0.374 AC: 409725 AN: 1096506

Other (OTH) AF: 0.315 AC: 18645 AN: 59238

GnomAD4 genome AF: 0.260 AC: 39624 AN: 152152 Hom.: 6463 Cov.: 35 AF XY: 0.259 AC XY: 19237 AN XY: 74378

African (AFR) AF: 0.0642 AC: 2667 AN: 41552

American (AMR) AF: 0.262 AC: 4008 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1094 AN: 5154

South Asian (SAS) AF: 0.268 AC: 1294 AN: 4824

European-Finnish (FIN) AF: 0.313 AC: 3307 AN: 10576

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25217 AN: 67966

Other (OTH) AF: 0.259 AC: 548 AN: 2114

Alfa AF: 0.303 Hom.: 2705

Bravo AF: 0.246

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.24
PhyloP100		-2.7
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

Other links and lift over

dbSNP: rs12303764; hg19: chr12-132399065; COSMIC: COSV58855657; COSMIC: COSV58855657;