NM_003062.4:c.4455G>T

Variant names:

• chr5-168666571-C-A
• rs1761053731
• NM_003062.4:c.4455G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003062.4(SLIT3):​c.4455G>T​(p.Gln1485His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLIT3 NM_003062.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37387455).

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.4455G>T	p.Gln1485His	missense	Exon 36 of 36	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.4476G>T	p.Gln1492His	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.4455G>T	p.Gln1485His	missense	Exon 36 of 36	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.4476G>T	p.Gln1492His	missense	Exon 36 of 36	ENSP00000332164.8	O75094-4
	ENSG00000254192	ENST00000520041.1	TSL:5	n.459C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	SLIT3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.026	D
Sift4G	Benign	0.081	T
Polyphen		0.94	P
Vest4		0.14
MutPred		0.25		Gain of catalytic residue at Q1485 (P = 0.0373)
MVP		0.68
MPC		0.63
ClinPred		0.91	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.21
Mutation Taster		=71/29	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: rs1761053731; hg19: chr5-168093576;