5-168669965-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003062.4(SLIT3):c.4154C>A(p.Thr1385Asn) 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. 16/21 in silico tools predict 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: 1.99

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08771664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLIT3	NM_003062.4	c.4154C>A	p.Thr1385Asn	missense_variant	35/36	ENST00000519560.6
SLIT3	NM_001271946.2	c.4175C>A	p.Thr1392Asn	missense_variant	35/36
SLIT3	XM_017009779.1	c.3965C>A	p.Thr1322Asn	missense_variant	35/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLIT3	ENST00000519560.6	c.4154C>A	p.Thr1385Asn	missense_variant	35/36	1	NM_003062.4	A1
SLIT3	ENST00000332966.8	c.4175C>A	p.Thr1392Asn	missense_variant	35/36	1		P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.4154C>A (p.T1385N) alteration is located in exon 35 (coding exon 35) of the SLIT3 gene. This alteration results from a C to A substitution at nucleotide position 4154, causing the threonine (T) at amino acid position 1385 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	12
Dann	Benign	0.65
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-0.48	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
REVEL	Benign	0.24
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.28, 0.28
MutPred		0.58		.;Loss of ubiquitination at K1381 (P = 0.0863);.;
MVP		0.30
MPC		0.33
ClinPred		0.042	T
GERP RS		4.3
Varity_R		0.042
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-168096970;