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5-168671230-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003062.4(SLIT3):c.4095T>C(p.Asp1365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,611,118 control chromosomes in the GnomAD database, including 55,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 7948 hom., cov: 33)
Exomes 𝑓: 0.25 ( 47357 hom. )

Consequence

SLIT3
NM_003062.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.52
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-168671230-A-G is Benign according to our data. Variant chr5-168671230-A-G is described in ClinVar as [Benign]. Clinvar id is 1268560.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.52 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLIT3NM_003062.4 linkuse as main transcriptc.4095T>C p.Asp1365= synonymous_variant 34/36 ENST00000519560.6
SLIT3NM_001271946.2 linkuse as main transcriptc.4116T>C p.Asp1372= synonymous_variant 34/36
SLIT3XM_017009779.1 linkuse as main transcriptc.3906T>C p.Asp1302= synonymous_variant 34/36

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLIT3ENST00000519560.6 linkuse as main transcriptc.4095T>C p.Asp1365= synonymous_variant 34/361 NM_003062.4 A1O75094-1
SLIT3ENST00000332966.8 linkuse as main transcriptc.4116T>C p.Asp1372= synonymous_variant 34/361 P4O75094-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.310
AC:
47052
AN:
151996
Hom.:
7924
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.437
Gnomad AMI
AF:
0.340
Gnomad AMR
AF:
0.362
Gnomad ASJ
AF:
0.165
Gnomad EAS
AF:
0.329
Gnomad SAS
AF:
0.155
Gnomad FIN
AF:
0.300
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.241
Gnomad OTH
AF:
0.270
GnomAD3 exomes
AF:
0.272
AC:
66878
AN:
245816
Hom.:
10143
AF XY:
0.256
AC XY:
34230
AN XY:
133664
show subpopulations
Gnomad AFR exome
AF:
0.443
Gnomad AMR exome
AF:
0.414
Gnomad ASJ exome
AF:
0.162
Gnomad EAS exome
AF:
0.324
Gnomad SAS exome
AF:
0.149
Gnomad FIN exome
AF:
0.302
Gnomad NFE exome
AF:
0.235
Gnomad OTH exome
AF:
0.244
GnomAD4 exome
AF:
0.248
AC:
362381
AN:
1459004
Hom.:
47357
Cov.:
39
AF XY:
0.244
AC XY:
176775
AN XY:
725452
show subpopulations
Gnomad4 AFR exome
AF:
0.438
Gnomad4 AMR exome
AF:
0.407
Gnomad4 ASJ exome
AF:
0.161
Gnomad4 EAS exome
AF:
0.347
Gnomad4 SAS exome
AF:
0.152
Gnomad4 FIN exome
AF:
0.301
Gnomad4 NFE exome
AF:
0.241
Gnomad4 OTH exome
AF:
0.247
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.310
AC:
47135
AN:
152114
Hom.:
7948
Cov.:
33
AF XY:
0.313
AC XY:
23290
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.437
Gnomad4 AMR
AF:
0.362
Gnomad4 ASJ
AF:
0.165
Gnomad4 EAS
AF:
0.330
Gnomad4 SAS
AF:
0.155
Gnomad4 FIN
AF:
0.300
Gnomad4 NFE
AF:
0.241
Gnomad4 OTH
AF:
0.268
Alfa
AF:
0.249
Hom.:
1622
Bravo
AF:
0.322
Asia WGS
AF:
0.232
AC:
810
AN:
3478
EpiCase
AF:
0.211
EpiControl
AF:
0.218

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 12, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
3.3
Dann
Benign
0.54

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: rs2277933; hg19: chr5-168098235; COSMIC: COSV60594699; COSMIC: COSV60594699; API