chr5-169100003-T-G

Variant names:

• chr5-169100003-T-G
• rs296000
• NM_003062.4:c.413+93476A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003062.4(SLIT3):​c.413+93476A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,206 control chromosomes in the GnomAD database, including 45,762 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 0.77 (45762 hom., cov: 33)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.413+93476A>C		intron_variant	Intron 4 of 35	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.413+93476A>C		intron_variant	Intron 4 of 35		NP_001258875.2
SLIT3	XM_017009779.1	c.224+93476A>C		intron_variant	Intron 4 of 35		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.413+93476A>C		intron_variant	Intron 4 of 35	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.413+93476A>C		intron_variant	Intron 4 of 35	1		ENSP00000332164.8
SLIT3	ENST00000518140.5	n.450+93476A>C		intron_variant	Intron 4 of 13	1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117806 AN: 152088 Hom.: 45716 Cov.: 33

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.775 AC: 117907 AN: 152206 Hom.: 45762 Cov.: 33 AF XY: 0.781 AC XY: 58102 AN XY: 74416

African (AFR) AF: 0.782 AC: 32455 AN: 41518

American (AMR) AF: 0.788 AC: 12061 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2445 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4618 AN: 5176

South Asian (SAS) AF: 0.782 AC: 3772 AN: 4824

European-Finnish (FIN) AF: 0.837 AC: 8871 AN: 10598

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51047 AN: 68002

Other (OTH) AF: 0.753 AC: 1591 AN: 2112

Alfa AF: 0.744 Hom.: 13605

Bravo AF: 0.771

Asia WGS AF: 0.832 AC: 2893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-2.6
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: rs296000; hg19: chr5-168527008;