5-168666571-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.4455G>T	p.Gln1485His	missense_variant	Exon 36 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4476G>T	p.Gln1492His	missense_variant	Exon 36 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.4266G>T	p.Gln1422His	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.4455G>T	p.Gln1485His	missense_variant	Exon 36 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4476G>T	p.Gln1492His	missense_variant	Exon 36 of 36	1		ENSP00000332164.8
ENSG00000254192	ENST00000520041.1	n.459C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLIT3-related disorder Uncertain:1

Nov 04, 2022

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The SLIT3 c.4476G>T variant is predicted to result in the amino acid substitution p.Gln1492His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	.;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.026	.;D;D
Sift4G	Benign	0.081	T;D;D
Polyphen		0.94	.;P;.
Vest4		0.14, 0.25
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

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: rs1761053731; hg19: chr5-168093576;