Variant chr5-168666683-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003062.4(SLIT3):c.4343C>T(p.Pro1448Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SLIT3
NM_003062.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

SLIT3 (HGNC:11087): (slit guidance ligand 3) The protein encoded by this gene is secreted, likely interacting with roundabout homolog receptors to effect cell migration. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

SLIT3 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0561741).

BS2

High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLIT3	NM_003062.4 linkuse as main transcript	c.4343C>T	p.Pro1448Leu	missense_variant	36/36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2 linkuse as main transcript	c.4364C>T	p.Pro1455Leu	missense_variant	36/36		NP_001258875.2
SLIT3	XM_017009779.1 linkuse as main transcript	c.4154C>T	p.Pro1385Leu	missense_variant	36/36		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6 linkuse as main transcript	c.4343C>T	p.Pro1448Leu	missense_variant	36/36	1	NM_003062.4	ENSP00000430333	A1	O75094-1
SLIT3	ENST00000332966.8 linkuse as main transcript	c.4364C>T	p.Pro1455Leu	missense_variant	36/36	1		ENSP00000332164	P4	O75094-4
	ENST00000520041.1 linkuse as main transcript	n.571G>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248950

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.4343C>T (p.P1448L) alteration is located in exon 36 (coding exon 36) of the SLIT3 gene. This alteration results from a C to T substitution at nucleotide position 4343, causing the proline (P) at amino acid position 1448 to be replaced by a leucine (L). 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

Benign

0.071

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.38

.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.26

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.4

.;D;D

REVEL

Benign

0.14

Sift

Benign

0.28

.;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.049, 0.071

MutPred

0.46

.;Loss of disorder (P = 0.0239);.;

MVP

0.18

MPC

0.29

ClinPred

0.040

GERP RS

2.1

Varity_R

0.049

gMVP

0.24

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

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