rs62376935

Positions:

• chr5-169263631-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003062.4(SLIT3):​c.198-12172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 495,762 control chromosomes in the GnomAD database, including 1,948 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (438 hom., cov: 27)
  • Exomes 𝑓: 0.076 (1510 hom.)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.198-12172G>A		intron_variant		ENST00000519560.6	NP_003053.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.198-12172G>A		intron_variant		1	NM_003062.4	ENSP00000430333.2

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9131 AN: 150516 Hom.: 441 Cov.: 27

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0647

GnomAD3 exomes AF: 0.0812 AC: 16719 AN: 205798 Hom.: 1199 AF XY: 0.0833 AC XY: 9463 AN XY: 113596

Gnomad AFR exome AF: 0.0339

Gnomad AMR exome AF: 0.0368

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.307

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0679

Gnomad OTH exome AF: 0.0822

GnomAD4 exome AF: 0.0761 AC: 26259 AN: 345128 Hom.: 1510 Cov.: 0 AF XY: 0.0795 AC XY: 15849 AN XY: 199478

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.0368

Gnomad4 ASJ exome AF: 0.0549

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0537

Gnomad4 NFE exome AF: 0.0662

Gnomad4 OTH exome AF: 0.0794

GnomAD4 genome AF: 0.0606 AC: 9128 AN: 150634 Hom.: 438 Cov.: 27 AF XY: 0.0630 AC XY: 4633 AN XY: 73526

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0600 Hom.: 162

Bravo AF: 0.0585

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
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

Other links and lift over

dbSNP: rs62376935; hg19: chr5-168690635; COSMIC: COSV60607362;