13-87676040-G-C

Variant names:

• chr13-87676040-G-C
• rs368289029
• NM_001384609.1:c.652G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384609.1(SLITRK5):​c.652G>C​(p.Val218Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V218M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLITRK5 NM_001384609.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

Genes affected

SLITRK5 (HGNC:20295): (SLIT and NTRK like family member 5) Members of the SLITRK family, such as SLITRK5, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1; MIM 603742). Most SLITRKs, including SLITRK5, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1; MIM 191315). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity (Aruga et al., 2003 [PubMed 14557068]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081632495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384609.1. 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
	SLITRK5	NM_001384609.1	MANE Select	c.652G>C	p.Val218Leu	missense	Exon 2 of 2	NP_001371538.1	O94991-1
	SLITRK5	NM_001384610.1		c.652G>C	p.Val218Leu	missense	Exon 2 of 2	NP_001371539.1	O94991-1
	SLITRK5	NM_015567.2		c.652G>C	p.Val218Leu	missense	Exon 2 of 2	NP_056382.1	O94991-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK5	ENST00000683689.1	MANE Select	c.652G>C	p.Val218Leu	missense	Exon 2 of 2	ENSP00000508338.1	O94991-1
	SLITRK5	ENST00000325089.7	TSL:1	c.652G>C	p.Val218Leu	missense	Exon 2 of 2	ENSP00000366283.2	O94991-1
	SLITRK5	ENST00000933099.1		c.652G>C	p.Val218Leu	missense	Exon 3 of 3	ENSP00000603158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.75
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.73	N
PhyloP100		1.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.082
Sift	Benign	0.44	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.43		Gain of helix (P = 0.132)
MVP		0.31
MPC		0.39
ClinPred		0.37	T
GERP RS		4.8
Varity_R		0.15
gMVP		0.36
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs368289029; hg19: chr13-88328295;