Genetic Variant SLITRK3:p.Val900Ala (chr3-165188132-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001318810.2(SLITRK3):c.2699T>C(p.Val900Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,474 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 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLITRK3
NM_001318810.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.100440025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK3	NM_001318810.2 link	c.2699T>C	p.Val900Ala	missense_variant	Exon 2 of 2	ENST00000475390.2	NP_001305739.1	O94933
SLITRK3	NM_001318811.2 link	c.2699T>C	p.Val900Ala	missense_variant	Exon 2 of 2		NP_001305740.1	O94933
SLITRK3	NM_014926.4 link	c.2699T>C	p.Val900Ala	missense_variant	Exon 2 of 2		NP_055741.2	O94933

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK3	ENST00000475390.2 link	c.2699T>C	p.Val900Ala	missense_variant	Exon 2 of 2	1	NM_001318810.2	ENSP00000420091.1		O94933
SLITRK3	ENST00000241274.3 link	c.2699T>C	p.Val900Ala	missense_variant	Exon 2 of 2	1		ENSP00000241274.3		O94933

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251042

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000274

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2699T>C (p.V900A) alteration is located in exon 2 (coding exon 1) of the SLITRK3 gene. This alteration results from a T to C substitution at nucleotide position 2699, causing the valine (V) at amino acid position 900 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.039

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.4

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.83

T;T

Polyphen

0.043

B;B

Vest4

0.098

MutPred

0.26

Gain of glycosylation at Y904 (P = 0.0048);Gain of glycosylation at Y904 (P = 0.0048);

MVP

0.76

MPC

0.57

ClinPred

0.58

GERP RS

5.8

Varity_R

0.22

gMVP

0.33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over