NM_003062.4:c.4247A>C

Variant names:

• chr5-168669872-T-G
• rs775669982
• NM_003062.4:c.4247A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003062.4(SLIT3):​c.4247A>C​(p.Lys1416Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: SLIT3 NM_003062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36017197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.4247A>C	p.Lys1416Thr	missense_variant	Exon 35 of 36	ENST00000519560.6	NP_003053.2
SLIT3	NM_001271946.2	c.4268A>C	p.Lys1423Thr	missense_variant	Exon 35 of 36		NP_001258875.2
SLIT3	XM_017009779.1	c.4058A>C	p.Lys1353Thr	missense_variant	Exon 35 of 36		XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.4247A>C	p.Lys1416Thr	missense_variant	Exon 35 of 36	1	NM_003062.4	ENSP00000430333.2
SLIT3	ENST00000332966.8	c.4268A>C	p.Lys1423Thr	missense_variant	Exon 35 of 36	1		ENSP00000332164.8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74356

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.
Eigen	Benign	-0.059
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.4	.;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.089	.;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.15	.;B;.
Vest4		0.35, 0.36
MutPred		0.44		.;Loss of methylation at K1416 (P = 6e-04);.;
MVP		0.53
MPC		0.41
ClinPred		0.69	D
GERP RS		4.0
Varity_R		0.10
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: rs775669982; hg19: chr5-168096877;