12-131897375-T-C

Position:

• chr12-131897375-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.246+1551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,152 control chromosomes in the GnomAD database, including 34,206 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 0.63 (34203 hom., cov: 33)
  • Exomes 𝑓: 0.80 (3 hom.)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK1	NM_003565.4	c.246+1551T>C		intron_variant		ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.246+1551T>C		intron_variant			XP_011537100.1
ULK1	XM_011538799.3	c.246+1551T>C		intron_variant			XP_011537101.1
ULK1	XR_007063134.1	n.626+1551T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.246+1551T>C		intron_variant		1	NM_003565.4	ENSP00000324560	P1
	ENST00000624048.1	n.876T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95650 AN: 152024 Hom.: 34210 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 NFE exome AF: 0.800

GnomAD4 genome AF: 0.629 AC: 95655 AN: 152142 Hom.: 34203 Cov.: 33 AF XY: 0.620 AC XY: 46105 AN XY: 74348

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.672

Alfa AF: 0.790 Hom.: 73429

Bravo AF: 0.613

Asia WGS AF: 0.489 AC: 1702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs9652059; hg19: chr12-132381920;