Variant chr5-168671219-C-T 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.4106G>A(p.Arg1369Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,609,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SLIT3
NM_003062.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.253

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:

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=0.04679063).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLIT3	NM_003062.4 linkuse as main transcript	c.4106G>A	p.Arg1369Gln	missense_variant	34/36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2 linkuse as main transcript	c.4127G>A	p.Arg1376Gln	missense_variant	34/36		NP_001258875.2
SLIT3	XM_017009779.1 linkuse as main transcript	c.3917G>A	p.Arg1306Gln	missense_variant	34/36		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6 linkuse as main transcript	c.4106G>A	p.Arg1369Gln	missense_variant	34/36	1	NM_003062.4	ENSP00000430333	A1	O75094-1
SLIT3	ENST00000332966.8 linkuse as main transcript	c.4127G>A	p.Arg1376Gln	missense_variant	34/36	1		ENSP00000332164	P4	O75094-4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000449

AC:

AN:

244830

Hom.:

AF XY:

0.0000600

AC XY:

AN XY:

133304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.0000941

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000398

AC:

AN:

1457632

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

724524

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.0000761

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000100

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 17, 2024

The c.4106G>A (p.R1369Q) alteration is located in exon 34 (coding exon 34) of the SLIT3 gene. This alteration results from a G to A substitution at nucleotide position 4106, causing the arginine (R) at amino acid position 1369 to be replaced by a glutamine (Q). 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

0.063

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.3

DANN

Benign

0.95

DEOGEN2

Benign

0.052

.;T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.39

T;T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.74

.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.21

.;N;N

REVEL

Benign

0.18

Sift

Benign

0.34

.;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.14, 0.099

MutPred

0.35

.;Loss of disorder (P = 0.2125);.;

MVP

0.39

MPC

0.32

ClinPred

0.023

GERP RS

0.51

Varity_R

0.036

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