12-131920888-G-T

Position:

• chr12-131920888-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ULK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK1	NM_003565.4	c.2962-212G>T		intron_variant		ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.3031-212G>T		intron_variant			XP_011537100.1
ULK1	XM_011538799.3	c.2944-212G>T		intron_variant			XP_011537101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.2962-212G>T		intron_variant		1	NM_003565.4	ENSP00000324560.3
ULK1	ENST00000540568.1	n.822G>T		non_coding_transcript_exon_variant	1/2	2
ULK1	ENST00000540647.5	n.831-212G>T		intron_variant		2
ULK1	ENST00000544718.1	n.897-212G>T		intron_variant		2

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

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0689

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0871

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.0598

Gnomad4 OTH exome AF: 0.0861

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

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0734

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0293 Hom.: 19

Bravo AF: 0.0957

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.82

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: rs12297124; hg19: chr12-132405433;