5-168669954-A-T

Variant names:

• chr5-168669954-A-T
• rs1462312638
• NM_003062.4:c.4165T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003062.4(SLIT3):​c.4165T>A​(p.Tyr1389Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 9.32

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.4165T>A	p.Tyr1389Asn	missense_variant	Exon 35 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4186T>A	p.Tyr1396Asn	missense_variant	Exon 35 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.3976T>A	p.Tyr1326Asn	missense_variant	Exon 35 of 36		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.4165T>A	p.Tyr1389Asn	missense_variant	Exon 35 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4186T>A	p.Tyr1396Asn	missense_variant	Exon 35 of 36	1		ENSP00000332164.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	.;D;.
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.68	D
MetaRNN	Pathogenic	0.99	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.7	.;H;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.6	.;D;D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	.;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.89, 0.90
MutPred		0.84		.;Gain of disorder (P = 0.0102);.;
MVP		0.95
MPC		1.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.88
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs1462312638; hg19: chr5-168096959;