3-165187953-G-C

Variant names:

• chr3-165187953-G-C
• rs1313094468
• NM_001318810.2:c.2878C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318810.2(SLITRK3):​c.2878C>G​(p.Leu960Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLITRK3 NM_001318810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.56
• Publications: 0 publications found

Genes affected

SLITRK3 (HGNC:23501): (SLIT and NTRK like family member 3) This gene encodes a member of the Slitrk family of structurally related transmembrane proteins that are involved in controlling neurite outgrowth. The encoded protein contains two leucine-rich repeat (LRR) domains and a C-terminal domain that is partially similar to Trk neurotrophin receptor protein. Enhanced expression of this gene was found in tissue from several different types of tumors. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Jan 2016]

SLITRK3 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24207848).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318810.2. 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
	SLITRK3	NM_001318810.2	MANE Select	c.2878C>G	p.Leu960Val	missense	Exon 2 of 2	NP_001305739.1	O94933
	SLITRK3	NM_001318811.2		c.2878C>G	p.Leu960Val	missense	Exon 2 of 2	NP_001305740.1	O94933
	SLITRK3	NM_014926.4		c.2878C>G	p.Leu960Val	missense	Exon 2 of 2	NP_055741.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK3	ENST00000475390.2	TSL:1 MANE Select	c.2878C>G	p.Leu960Val	missense	Exon 2 of 2	ENSP00000420091.1	O94933
	SLITRK3	ENST00000241274.3	TSL:1	c.2878C>G	p.Leu960Val	missense	Exon 2 of 2	ENSP00000241274.3	O94933
	SLITRK3	ENST00000925264.1		c.2878C>G	p.Leu960Val	missense	Exon 2 of 2	ENSP00000595323.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251450 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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.36	B
Vest4		0.33
MutPred		0.28		Gain of glycosylation at T962 (P = 0.0167)
MVP		0.80
MPC		0.78
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.42
gMVP		0.26
Mutation Taster		=63/37	polymorphism

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: rs1313094468; hg19: chr3-164905741;