chr12-131912058-C-T

Variant names:

• chr12-131912058-C-T
• rs11616018
• NM_003565.4:c.1065C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003565.4(ULK1):​c.1065C>T​(p.Asp355Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,612,128 control chromosomes in the GnomAD database, including 497,343 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 0.66 (36405 hom., cov: 35)
  • Exomes 𝑓: 0.79 (460938 hom.)
• Consequence: ULK1 NM_003565.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 24 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK1	NM_003565.4	c.1065C>T	p.Asp355Asp	synonymous_variant	Exon 13 of 28	ENST00000321867.6	NP_003556.2
ULK1	XM_011538798.4	c.1065C>T	p.Asp355Asp	synonymous_variant	Exon 13 of 28		XP_011537100.1
ULK1	XM_011538799.3	c.1065C>T	p.Asp355Asp	synonymous_variant	Exon 13 of 28		XP_011537101.1
ULK1	XR_007063134.1	n.1445C>T		non_coding_transcript_exon_variant	Exon 13 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK1	ENST00000321867.6	c.1065C>T	p.Asp355Asp	synonymous_variant	Exon 13 of 28	1	NM_003565.4	ENSP00000324560.3

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100411 AN: 152102 Hom.: 36407 Cov.: 35

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.706

GnomAD2 exomes AF: 0.711 AC: 176460 AN: 248156 AF XY: 0.723

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.681

Gnomad ASJ exome AF: 0.772

Gnomad EAS exome AF: 0.354

Gnomad FIN exome AF: 0.693

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.766

GnomAD4 exome AF: 0.786 AC: 1148007 AN: 1459908 Hom.: 460938 Cov.: 79 AF XY: 0.786 AC XY: 570652 AN XY: 726212

African (AFR) AF: 0.353 AC: 11814 AN: 33460

American (AMR) AF: 0.686 AC: 30571 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 20054 AN: 26130

East Asian (EAS) AF: 0.342 AC: 13576 AN: 39688

South Asian (SAS) AF: 0.705 AC: 60745 AN: 86194

European-Finnish (FIN) AF: 0.706 AC: 36806 AN: 52136

Middle Eastern (MID) AF: 0.808 AC: 4660 AN: 5766

European-Non Finnish (NFE) AF: 0.832 AC: 924620 AN: 1111638

Other (OTH) AF: 0.748 AC: 45161 AN: 60350

GnomAD4 genome AF: 0.660 AC: 100432 AN: 152220 Hom.: 36405 Cov.: 35 AF XY: 0.652 AC XY: 48530 AN XY: 74414

African (AFR) AF: 0.366 AC: 15217 AN: 41524

American (AMR) AF: 0.731 AC: 11185 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2636 AN: 3468

East Asian (EAS) AF: 0.357 AC: 1845 AN: 5170

South Asian (SAS) AF: 0.690 AC: 3333 AN: 4828

European-Finnish (FIN) AF: 0.679 AC: 7194 AN: 10602

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56458 AN: 68012

Other (OTH) AF: 0.706 AC: 1493 AN: 2114

Alfa AF: 0.770 Hom.: 80367

Bravo AF: 0.650

Asia WGS AF: 0.509 AC: 1771 AN: 3478

EpiCase AF: 0.831

EpiControl AF: 0.834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.054
DANN	Benign	0.77
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs11616018; hg19: chr12-132396603; COSMIC: COSV58857236; COSMIC: COSV58857236;