5-168666554-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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]

ENSG00000254192 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.4472G>T	p.Arg1491Leu	missense_variant	Exon 36 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4493G>T	p.Arg1498Leu	missense_variant	Exon 36 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.4283G>T	p.Arg1428Leu	missense_variant	Exon 36 of 36		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.4472G>T	p.Arg1491Leu	missense_variant	Exon 36 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4493G>T	p.Arg1498Leu	missense_variant	Exon 36 of 36	1		ENSP00000332164.8
ENSG00000254192	ENST00000520041.1	n.442C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Uncertain	0.029	D
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	.;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.017	.;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.52, 0.67
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-168093559;