13-87675407-C-T

Position:

• chr13-87675407-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384609.1(SLITRK5):​c.19C>T​(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLITRK5 NM_001384609.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099791616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK5	NM_001384609.1	c.19C>T	p.Pro7Ser	missense_variant	2/2	ENST00000683689.1	NP_001371538.1
SLITRK5	NM_001384610.1	c.19C>T	p.Pro7Ser	missense_variant	2/2		NP_001371539.1
SLITRK5	NM_015567.2	c.19C>T	p.Pro7Ser	missense_variant	2/2		NP_056382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLITRK5	ENST00000683689.1	c.19C>T	p.Pro7Ser	missense_variant	2/2		NM_001384609.1	ENSP00000508338.1
SLITRK5	ENST00000325089.7	c.19C>T	p.Pro7Ser	missense_variant	2/2	1		ENSP00000366283.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461686 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727118

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.19C>T (p.P7S) alteration is located in exon 2 (coding exon 1) of the SLITRK5 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.095
Sift	Benign	0.069	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.082
MPC		0.40
ClinPred		0.089	T
GERP RS		3.9
Varity_R		0.065
gMVP		0.75

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: rs1877227162; hg19: chr13-88327662;