rs12654448

Variant names:

• chr5-169054766-C-T
• rs12654448
• NM_003062.4:c.413+138713G>A

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+138713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,154 control chromosomes in the GnomAD database, including 1,627 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 0.13 (1627 hom., cov: 32)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 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+138713G>A		intron	N/A	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.413+138713G>A		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+138713G>A		intron	N/A	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.413+138713G>A		intron	N/A	ENSP00000332164.8	O75094-4
	SLIT3	ENST00000518140.5	TSL:1	n.450+138713G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19313 AN: 152036 Hom.: 1625 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.127 AC: 19323 AN: 152154 Hom.: 1627 Cov.: 32 AF XY: 0.131 AC XY: 9745 AN XY: 74390

African (AFR) AF: 0.185 AC: 7667 AN: 41480

American (AMR) AF: 0.110 AC: 1675 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2175 AN: 5168

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4826

European-Finnish (FIN) AF: 0.123 AC: 1303 AN: 10584

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0800 AC: 5445 AN: 68020

Other (OTH) AF: 0.118 AC: 249 AN: 2114

Alfa AF: 0.106 Hom.: 155

Bravo AF: 0.131

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.65
PhyloP100		-0.17
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: rs12654448; hg19: chr5-168481771; COSMIC: COSV60599925;