5-168666683-G-T

Variant names:

• chr5-168666683-G-T
• NM_003062.4:c.4343C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003062.4(SLIT3):​c.4343C>A​(p.Pro1448Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLIT3 NM_003062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06463903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.4343C>A	p.Pro1448Gln	missense_variant	Exon 36 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4364C>A	p.Pro1455Gln	missense_variant	Exon 36 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.4154C>A	p.Pro1385Gln	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.4343C>A	p.Pro1448Gln	missense_variant	Exon 36 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4364C>A	p.Pro1455Gln	missense_variant	Exon 36 of 36	1		ENSP00000332164.8
ENSG00000254192	ENST00000520041.1	n.571G>T		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.15	.;T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.18	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Benign	0.10
Sift	Benign	0.24	.;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0030	.;B;.
Vest4		0.075, 0.099
MutPred		0.37		.;Loss of catalytic residue at P1448 (P = 0.0123);.;
MVP		0.43
MPC		0.26
ClinPred		0.061	T
GERP RS		2.1
Varity_R		0.041
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-168093688;