rs4282339

Variant names:

• chr5-168829235-G-A
• rs4282339
• NM_003062.4:c.558-5904C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003062.4(SLIT3):​c.558-5904C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,234 control chromosomes in the GnomAD database, including 2,856 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 0.19 (2856 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 57 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.558-5904C>T		intron_variant	Intron 6 of 35	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.558-5904C>T		intron_variant	Intron 6 of 35		NP_001258875.2
SLIT3	XM_017009779.1	c.369-5904C>T		intron_variant	Intron 6 of 35		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.558-5904C>T		intron_variant	Intron 6 of 35	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.558-5904C>T		intron_variant	Intron 6 of 35	1		ENSP00000332164.8
SLIT3	ENST00000518140.5	n.595-5904C>T		intron_variant	Intron 6 of 13	1
SLIT3	ENST00000521150.1	n.250-5904C>T		intron_variant	Intron 1 of 7	2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28355 AN: 152116 Hom.: 2855 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28372 AN: 152234 Hom.: 2856 Cov.: 32 AF XY: 0.188 AC XY: 14008 AN XY: 74452

African (AFR) AF: 0.143 AC: 5954 AN: 41530

American (AMR) AF: 0.178 AC: 2716 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3468

East Asian (EAS) AF: 0.186 AC: 962 AN: 5184

South Asian (SAS) AF: 0.311 AC: 1503 AN: 4828

European-Finnish (FIN) AF: 0.187 AC: 1985 AN: 10606

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13740 AN: 68000

Other (OTH) AF: 0.189 AC: 399 AN: 2114

Alfa AF: 0.201 Hom.: 15374

Bravo AF: 0.179

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.75
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4282339; hg19: chr5-168256240;