5-168712307-T-C

Variant names:

• chr5-168712307-T-C
• NM_003062.4:c.2531A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003062.4(SLIT3):​c.2531A>G​(p.Asn844Ser) 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. 17/22 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: 1.10
• Publications: 0 publications found

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]

SLIT3-AS2 (HGNC:40551): (SLIT3 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065209895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	NM_003062.4	MANE Select	c.2531A>G	p.Asn844Ser	missense	Exon 24 of 36	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.2531A>G	p.Asn844Ser	missense	Exon 24 of 36	NP_001258875.2	O75094-4
	SLIT3-AS2	NR_130737.1		n.721T>C		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	ENST00000519560.6	TSL:1 MANE Select	c.2531A>G	p.Asn844Ser	missense	Exon 24 of 36	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.2531A>G	p.Asn844Ser	missense	Exon 24 of 36	ENSP00000332164.8	O75094-4
	SLIT3-AS2	ENST00000522615.1	TSL:2	n.2250T>C		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.71	N
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Benign	0.42	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.43		Gain of disorder (P = 0.0436)
MVP		0.30
MPC		0.22
ClinPred		0.25	T
GERP RS		0.14
Varity_R		0.090
gMVP		0.20
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr5-168139312;