chr12-131899081-A-C

Variant names:

• chr12-131899081-A-C
• rs7133672
• NM_003565.4:c.246+3257A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003565.4(ULK1):​c.246+3257A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: ULK1 NM_003565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4	c.246+3257A>C		intron_variant	Intron 3 of 27	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.246+3257A>C		intron_variant	Intron 3 of 27		XP_011537100.1
ULK1	XM_011538799.3	c.246+3257A>C		intron_variant	Intron 3 of 27		XP_011537101.1
ULK1	XR_007063134.1	n.626+3257A>C		intron_variant	Intron 3 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.246+3257A>C		intron_variant	Intron 3 of 27	1	NM_003565.4	ENSP00000324560.3

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.17
PhyloP100		-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

Other links and lift over

dbSNP: rs7133672; hg19: chr12-132383626;