chr5-168666520-C-T

Variant names:

• chr5-168666520-C-T
• rs143047334
• NM_003062.4:c.4506G>A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003062.4(SLIT3):​c.4506G>A​(p.Thr1502Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,611,708 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (24 hom.)
• Consequence: SLIT3 NM_003062.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -4.36

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]

ENSG00000254192 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 5-168666520-C-T is Benign according to our data. Variant chr5-168666520-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.36 with no splicing effect.
• BS2: High AC in GnomAd4 at 532 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.4506G>A	p.Thr1502Thr	synonymous_variant	Exon 36 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4527G>A	p.Thr1509Thr	synonymous_variant	Exon 36 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.4317G>A	p.Thr1439Thr	synonymous_variant	Exon 36 of 36		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.4506G>A	p.Thr1502Thr	synonymous_variant	Exon 36 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4527G>A	p.Thr1509Thr	synonymous_variant	Exon 36 of 36	1		ENSP00000332164.8
ENSG00000254192	ENST00000520041.1	n.408C>T		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 532 AN: 152208 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00503

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00291 AC: 725 AN: 248876 Hom.: 3 AF XY: 0.00264 AC XY: 356 AN XY: 134662

Gnomad AFR exome AF: 0.00334

Gnomad AMR exome AF: 0.000726

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00234

Gnomad NFE exome AF: 0.00515

Gnomad OTH exome AF: 0.00296

GnomAD4 exome AF: 0.00490 AC: 7144 AN: 1459382 Hom.: 24 Cov.: 32 AF XY: 0.00465 AC XY: 3372 AN XY: 725840

Gnomad4 AFR exome AF: 0.00410

Gnomad4 AMR exome AF: 0.000761

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00246

Gnomad4 NFE exome AF: 0.00585

Gnomad4 OTH exome AF: 0.00561

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152326 Hom.: 3 Cov.: 33 AF XY: 0.00307 AC XY: 229 AN XY: 74486

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00503

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00424 Hom.: 2

Bravo AF: 0.00357

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00398

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

SLIT3-related disorder Benign:1

Dec 30, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLIT3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.19
DANN	Benign	0.83

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: rs143047334; hg19: chr5-168093525;