5-168666554-C-A

Variant names:

• chr5-168666554-C-A
• rs140403495
• NM_003062.4:c.4472G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003062.4(SLIT3):​c.4472G>T​(p.Arg1491Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1491C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLIT3 NM_003062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12
• Publications: 0 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

ENSG00000254192 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4472G>T	p.Arg1491Leu	missense	Exon 36 of 36	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.4493G>T	p.Arg1498Leu	missense	Exon 36 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.4472G>T	p.Arg1491Leu	missense	Exon 36 of 36	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.4493G>T	p.Arg1498Leu	missense	Exon 36 of 36	ENSP00000332164.8	O75094-4
	ENSG00000254192	ENST00000520041.1	TSL:5	n.442C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.029	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.43		Loss of MoRF binding (P = 0.011)
MVP		0.91
MPC		0.56
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.41
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140403495; hg19: chr5-168093559;