chr12-131920888-G-T

Variant names:

• chr12-131920888-G-T
• rs12297124
• NM_003565.4:c.2962-212G>T

Variant summary

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

The NM_003565.4(ULK1):​c.2962-212G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 642,326 control chromosomes in the GnomAD database, including 2,961 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 0.10 (1059 hom., cov: 33)
  • Exomes 𝑓: 0.078 (1902 hom.)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 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.2962-212G>T		intron	N/A	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.2962-212G>T		intron	N/A	ENSP00000324560.3	O75385
	ULK1	ENST00000939866.1		c.3031-212G>T		intron	N/A	ENSP00000609925.1
	ULK1	ENST00000939867.1		c.2959-212G>T		intron	N/A	ENSP00000609926.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15808 AN: 152040 Hom.: 1059 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0851

GnomAD4 exome AF: 0.0782 AC: 38309 AN: 490168 Hom.: 1902 Cov.: 6 AF XY: 0.0794 AC XY: 19982 AN XY: 251732

African (AFR) AF: 0.166 AC: 2217 AN: 13320

American (AMR) AF: 0.0689 AC: 1167 AN: 16928

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 1725 AN: 13064

East Asian (EAS) AF: 0.0871 AC: 2635 AN: 30244

South Asian (SAS) AF: 0.112 AC: 4153 AN: 36938

European-Finnish (FIN) AF: 0.168 AC: 4609 AN: 27478

Middle Eastern (MID) AF: 0.0888 AC: 179 AN: 2016

European-Non Finnish (NFE) AF: 0.0598 AC: 19340 AN: 323666

Other (OTH) AF: 0.0861 AC: 2284 AN: 26514

GnomAD4 genome AF: 0.104 AC: 15825 AN: 152158 Hom.: 1059 Cov.: 33 AF XY: 0.109 AC XY: 8126 AN XY: 74380

African (AFR) AF: 0.164 AC: 6800 AN: 41502

American (AMR) AF: 0.0679 AC: 1037 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3466

East Asian (EAS) AF: 0.0734 AC: 380 AN: 5174

South Asian (SAS) AF: 0.108 AC: 520 AN: 4818

European-Finnish (FIN) AF: 0.201 AC: 2127 AN: 10586

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4237 AN: 68010

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0293 Hom.: 19

Bravo AF: 0.0957

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		-0.068
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: rs12297124; hg19: chr12-132405433;