chr15-74838287-C-G

Variant names:

• chr15-74838287-C-G
• rs1008991958
• NM_001099436.4:c.1225G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001099436.4(ULK3):​c.1225G>C​(p.Glu409Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,410,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ULK3 NM_001099436.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36
• Publications: 0 publications found

Genes affected

ULK3 (HGNC:19703): (unc-51 like kinase 3) Enables protein serine/threonine kinase activity. Involved in several processes, including fibroblast activation; protein autophosphorylation; and regulation of smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099436.4. 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
	ULK3	NM_001099436.4	MANE Select	c.1225G>C	p.Glu409Gln	missense	Exon 12 of 16	NP_001092906.3	Q6PHR2-1
	ULK3	NM_001411082.1		c.1258G>C	p.Glu420Gln	missense	Exon 12 of 16	NP_001398011.1	Q6PHR2-4
	ULK3	NM_001284364.3		c.1225G>C	p.Glu409Gln	missense	Exon 12 of 16	NP_001271293.2	Q6PHR2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK3	ENST00000440863.7	TSL:2 MANE Select	c.1225G>C	p.Glu409Gln	missense	Exon 12 of 16	ENSP00000400312.2	Q6PHR2-1
	ULK3	ENST00000569437.5	TSL:1	c.1225G>C	p.Glu409Gln	missense	Exon 12 of 16	ENSP00000456051.1	Q6PHR2-3
	ULK3	ENST00000566479.5	TSL:1	n.1430G>C		non_coding_transcript_exon	Exon 11 of 15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 168688 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410200 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 696806

African (AFR) AF: 0.0000312 AC: 1 AN: 32072

American (AMR) AF: 0.00 AC: 0 AN: 37272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25314

East Asian (EAS) AF: 0.00 AC: 0 AN: 36410

South Asian (SAS) AF: 0.00 AC: 0 AN: 80000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085436

Other (OTH) AF: 0.00 AC: 0 AN: 58396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.43
Sift	Benign	0.56	T
Sift4G	Benign	0.59	T
Polyphen		0.99	D
Vest4		0.53
MutPred		0.53		Loss of phosphorylation at S417 (P = 0.1334)
MVP		0.85
MPC		0.89
ClinPred		0.87	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1008991958; hg19: chr15-75130628;