Variant 5-168666474-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003062.4(SLIT3):c.4552G>A(p.Gly1518Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,582,344 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SLIT3
NM_003062.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLIT3	NM_003062.4 linkuse as main transcript	c.4552G>A	p.Gly1518Ser	missense_variant	36/36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2 linkuse as main transcript	c.4573G>A	p.Gly1525Ser	missense_variant	36/36		NP_001258875.2
SLIT3	XM_017009779.1 linkuse as main transcript	c.4363G>A	p.Gly1455Ser	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.4552G>A	p.Gly1518Ser	missense_variant	36/36	1	NM_003062.4	ENSP00000430333	A1	O75094-1
SLIT3	ENST00000332966.8 linkuse as main transcript	c.4573G>A	p.Gly1525Ser	missense_variant	36/36	1		ENSP00000332164	P4	O75094-4
	ENST00000520041.1 linkuse as main transcript	n.362C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152094

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

233296

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

125520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.000101

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

171

AN:

1430250

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

706726

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.0000697

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000484

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.0000850

GnomAD4 genome

AF:

0.000105

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74286

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000978

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

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

Jun 21, 2023

The c.4552G>A (p.G1518S) alteration is located in exon 36 (coding exon 36) of the SLIT3 gene. This alteration results from a G to A substitution at nucleotide position 4552, causing the glycine (G) at amino acid position 1518 to be replaced by a serine (S). 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

0.087

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

.;T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.7

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.7

.;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0050

.;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.47, 0.55

MVP

0.64

MPC

0.83

ClinPred

0.63

GERP RS

5.4

Varity_R

0.52

gMVP

0.37

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