rs148053357

Variant names:

• chr3-165188232-C-A
• rs148053357
• NM_001318810.2:c.2599G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001318810.2(SLITRK3):​c.2599G>T​(p.Gly867Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000706 in 1,613,662 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: 𝑓 0.00036 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: SLITRK3 NM_001318810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.31
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21022126).

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.2599G>T	p.Gly867Cys	missense	Exon 2 of 2	NP_001305739.1	O94933
	SLITRK3	NM_001318811.2		c.2599G>T	p.Gly867Cys	missense	Exon 2 of 2	NP_001305740.1	O94933
	SLITRK3	NM_014926.4		c.2599G>T	p.Gly867Cys	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.2599G>T	p.Gly867Cys	missense	Exon 2 of 2	ENSP00000420091.1	O94933
	SLITRK3	ENST00000241274.3	TSL:1	c.2599G>T	p.Gly867Cys	missense	Exon 2 of 2	ENSP00000241274.3	O94933
	SLITRK3	ENST00000925264.1		c.2599G>T	p.Gly867Cys	missense	Exon 2 of 2	ENSP00000595323.1

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 55 AN: 151740 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000482

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251378 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461806 Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25 AN XY: 727200

African (AFR) AF: 0.000926 AC: 31 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111970

Other (OTH) AF: 0.000182 AC: 11 AN: 60394

GnomAD4 genome AF: 0.000362 AC: 55 AN: 151856 Hom.: 0 Cov.: 31 AF XY: 0.000458 AC XY: 34 AN XY: 74252

African (AFR) AF: 0.00123 AC: 51 AN: 41406

American (AMR) AF: 0.000197 AC: 3 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67924

Other (OTH) AF: 0.000477 AC: 1 AN: 2098

Alfa AF: 0.000304 Hom.: 0

Bravo AF: 0.000412

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000123 AC: 15

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Benign	-0.0091	T
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.61	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.67
MVP		0.67
MPC		0.79
ClinPred		0.17	T
GERP RS		5.8
Varity_R		0.30
gMVP		0.42
Mutation Taster		=85/15	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: rs148053357; hg19: chr3-164906020; COSMIC: COSV53846894; COSMIC: COSV53846894;