NM_003062.4:c.413+64289A>T

Variant names:

• chr5-169129190-T-A
• rs9688032
• NM_003062.4:c.413+64289A>T

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+64289A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,952 control chromosomes in the GnomAD database, including 10,019 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 0.36 (10019 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 6 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]

SLIT3 Gene-Disease associations (from GenCC):

• congenital diaphragmatic hernia

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ENSG00000302955 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	NM_003062.4	MANE Select	c.413+64289A>T		intron	N/A	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.413+64289A>T		intron	N/A	NP_001258875.2	O75094-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	ENST00000519560.6	TSL:1 MANE Select	c.413+64289A>T		intron	N/A	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.413+64289A>T		intron	N/A	ENSP00000332164.8	O75094-4
	SLIT3	ENST00000518140.5	TSL:1	n.450+64289A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54513 AN: 151832 Hom.: 10001 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.359 AC: 54568 AN: 151952 Hom.: 10019 Cov.: 32 AF XY: 0.360 AC XY: 26745 AN XY: 74270

African (AFR) AF: 0.432 AC: 17886 AN: 41402

American (AMR) AF: 0.334 AC: 5104 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1300 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2446 AN: 5162

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4806

European-Finnish (FIN) AF: 0.356 AC: 3759 AN: 10558

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21457 AN: 67966

Other (OTH) AF: 0.367 AC: 774 AN: 2110

Alfa AF: 0.354 Hom.: 1170

Bravo AF: 0.358

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.84
DANN	Benign	0.52
PhyloP100		-0.18
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: rs9688032; hg19: chr5-168556195;