rs180813266

Variant names:

• chr5-168669798-C-T
• rs180813266
• NM_003062.4:c.4321G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003062.4(SLIT3):​c.4321G>A​(p.Glu1441Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: SLIT3 NM_003062.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17518845).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.4321G>A	p.Glu1441Lys	missense	Exon 35 of 36	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.4342G>A	p.Glu1448Lys	missense	Exon 35 of 36	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.4321G>A	p.Glu1441Lys	missense	Exon 35 of 36	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.4342G>A	p.Glu1448Lys	missense	Exon 35 of 36	ENSP00000332164.8	O75094-4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 11 AN: 250548 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1461270 Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28 AN XY: 726940

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000188 AC: 1 AN: 5308

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111984

Other (OTH) AF: 0.0000663 AC: 4 AN: 60342

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74470

African (AFR) AF: 0.0000241 AC: 1 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.56	T
Polyphen		0.54	P
Vest4		0.56
MVP		0.74
MPC		0.39
ClinPred		0.11	T
GERP RS		2.3
Varity_R		0.046
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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: rs180813266; hg19: chr5-168096803; COSMIC: COSV60608591; COSMIC: COSV60608591;