rs755151716

Variant names:

• chr15-74838703-C-A
• rs755151716
• NM_001099436.4:c.1042G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-74838703-C-A
• chr15-74838703-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099436.4(ULK3):​c.1042G>T​(p.Val348Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,314 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V348I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ULK3 NM_001099436.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK3	NM_001099436.4	c.1042G>T	p.Val348Phe	missense_variant	Exon 10 of 16	ENST00000440863.7	NP_001092906.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK3	ENST00000440863.7	c.1042G>T	p.Val348Phe	missense_variant	Exon 10 of 16	2	NM_001099436.4	ENSP00000400312.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000815 AC: 2 AN: 245542 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133608

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 SAS exome AF: 0.0000663

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460314 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.091	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.67	P;P;.
Vest4		0.55
MutPred		0.48		.;.;Loss of MoRF binding (P = 0.0829);
MVP		0.61
MPC		0.97
ClinPred		0.72	D
GERP RS		5.3
Varity_R		0.26
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs755151716; hg19: chr15-75131044;