5-168671245-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003062.4(SLIT3):c.4080C>T(p.Thr1360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,612,782 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (14 hom.)
• Consequence: SLIT3 NM_003062.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.96

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-168671245-G-A is Benign according to our data. Variant chr5-168671245-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.96 with no splicing effect.
• BS2: High AC in GnomAd at 348 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLIT3	NM_003062.4	c.4080C>T	p.Thr1360=	synonymous_variant	34/36	ENST00000519560.6
SLIT3	NM_001271946.2	c.4101C>T	p.Thr1367=	synonymous_variant	34/36
SLIT3	XM_017009779.1	c.3891C>T	p.Thr1297=	synonymous_variant	34/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLIT3	ENST00000519560.6	c.4080C>T	p.Thr1360=	synonymous_variant	34/36	1	NM_003062.4	A1
SLIT3	ENST00000332966.8	c.4101C>T	p.Thr1367=	synonymous_variant	34/36	1		P4

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 348 AN: 152226 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00274 AC: 677 AN: 247300 Hom.: 2 AF XY: 0.00299 AC XY: 402 AN XY: 134316

Gnomad AFR exome AF: 0.000444

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00157

Gnomad FIN exome AF: 0.00117

Gnomad NFE exome AF: 0.00358

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00286 AC: 4183 AN: 1460438 Hom.: 14 Cov.: 38 AF XY: 0.00298 AC XY: 2163 AN XY: 726458

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00169

Gnomad4 FIN exome AF: 0.00170

Gnomad4 NFE exome AF: 0.00292

Gnomad4 OTH exome AF: 0.00342

GnomAD4 genome AF: 0.00229 AC: 349 AN: 152344 Hom.: 2 Cov.: 33 AF XY: 0.00211 AC XY: 157 AN XY: 74492

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00317

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00358 Hom.: 2

Bravo AF: 0.00229

EpiCase AF: 0.00458

EpiControl AF: 0.00593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	SLIT3: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.71
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs150953871; hg19: chr5-168098250; COSMIC: COSV100267629; COSMIC: COSV100267629;