chr5-168711055-C-T

Variant names:

• chr5-168711055-C-T
• rs141936653
• NM_003062.4:c.2559G>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.2559G>A​(p.Ala853Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,576,470 control chromosomes in the GnomAD database, including 52 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 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (37 hom.)
• Consequence: SLIT3 NM_003062.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.40

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)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-168711055-C-T is Benign according to our data. Variant chr5-168711055-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.4 with no splicing effect.
• BS2: High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.2559G>A	p.Ala853Ala	synonymous_variant	Exon 25 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.2559G>A	p.Ala853Ala	synonymous_variant	Exon 25 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.2370G>A	p.Ala790Ala	synonymous_variant	Exon 25 of 36		XP_016865268.1
SLIT3-AS2	NR_130737.1	n.698+855C>T		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.2559G>A	p.Ala853Ala	synonymous_variant	Exon 25 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.2559G>A	p.Ala853Ala	synonymous_variant	Exon 25 of 36	1		ENSP00000332164.8
SLIT3-AS2	ENST00000522615.1	n.2227+855C>T		intron_variant	Intron 2 of 5	2

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 527 AN: 152160 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00406 AC: 832 AN: 204902 Hom.: 18 AF XY: 0.00401 AC XY: 442 AN XY: 110354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000782

Gnomad SAS exome AF: 0.0000411

Gnomad FIN exome AF: 0.0393

Gnomad NFE exome AF: 0.000971

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00177 AC: 2515 AN: 1424192 Hom.: 37 Cov.: 32 AF XY: 0.00175 AC XY: 1231 AN XY: 705090

Gnomad4 AFR exome AF: 0.000124

Gnomad4 AMR exome AF: 0.0000241

Gnomad4 ASJ exome AF: 0.0000800

Gnomad4 EAS exome AF: 0.000533

Gnomad4 SAS exome AF: 0.0000499

Gnomad4 FIN exome AF: 0.0384

Gnomad4 NFE exome AF: 0.000360

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00345 AC: 526 AN: 152278 Hom.: 15 Cov.: 32 AF XY: 0.00505 AC XY: 376 AN XY: 74452

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00119 Hom.: 0

Bravo AF: 0.000261

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

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	-0.79
CADD	Benign	0.13
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141936653; hg19: chr5-168138060;