NM_003062.4:c.4361T>C

Variant names:

• chr5-168666665-A-G
• rs146090354
• NM_003062.4:c.4361T>C

Variant summary

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

The NM_003062.4(SLIT3):​c.4361T>C​(p.Val1454Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLIT3 NM_003062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40

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.4361T>C	p.Val1454Ala	missense_variant	Exon 36 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4382T>C	p.Val1461Ala	missense_variant	Exon 36 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.4172T>C	p.Val1391Ala	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.4361T>C	p.Val1454Ala	missense_variant	Exon 36 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4382T>C	p.Val1461Ala	missense_variant	Exon 36 of 36	1		ENSP00000332164.8
ENSG00000254192	ENST00000520041.1	n.553A>G		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	.;T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	.;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0070	.;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.97	.;D;.
Vest4		0.30, 0.36
MutPred		0.57		.;Gain of disorder (P = 0.073);.;
MVP		0.52
MPC		0.52
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.30
gMVP		0.59

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: rs146090354; hg19: chr5-168093670;