5-168710971-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003062.4(SLIT3):​c.2643C>T​(p.Ile881Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,566,942 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SLIT3
NM_003062.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.587
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-AS2 (HGNC:40551): (SLIT3 antisense RNA 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 5-168710971-G-A is Benign according to our data. Variant chr5-168710971-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2498992.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.587 with no splicing effect.
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLIT3NM_003062.4 linkc.2643C>T p.Ile881Ile synonymous_variant Exon 25 of 36 ENST00000519560.6 NP_003053.2 O75094-1
SLIT3NM_001271946.2 linkc.2643C>T p.Ile881Ile synonymous_variant Exon 25 of 36 NP_001258875.2 O75094-4
SLIT3XM_017009779.1 linkc.2454C>T p.Ile818Ile synonymous_variant Exon 25 of 36 XP_016865268.1
SLIT3-AS2NR_130737.1 linkn.698+771G>A intron_variant Intron 3 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLIT3ENST00000519560.6 linkc.2643C>T p.Ile881Ile synonymous_variant Exon 25 of 36 1 NM_003062.4 ENSP00000430333.2 O75094-1
SLIT3ENST00000332966.8 linkc.2643C>T p.Ile881Ile synonymous_variant Exon 25 of 36 1 ENSP00000332164.8 O75094-4
SLIT3-AS2ENST00000522615.1 linkn.2227+771G>A intron_variant Intron 2 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000285
AC:
5
AN:
175632
Hom.:
0
AF XY:
0.0000430
AC XY:
4
AN XY:
92998
show subpopulations
Gnomad AFR exome
AF:
0.000188
Gnomad AMR exome
AF:
0.0000378
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:
0.0000278
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
31
AN:
1414760
Hom.:
0
Cov.:
32
AF XY:
0.0000272
AC XY:
19
AN XY:
699016
show subpopulations
Gnomad4 AFR exome
AF:
0.000153
Gnomad4 AMR exome
AF:
0.0000265
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000166
Gnomad4 OTH exome
AF:
0.000102
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.000169
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SLIT3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
1.3
DANN
Benign
0.88

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.

Other links and lift over

dbSNP: rs758437974; hg19: chr5-168137976; COSMIC: COSV60605754; COSMIC: COSV60605754; API