X-145823009-T-C

Variant names:

• chrX-145823009-T-C
• NM_032539.5:c.584T>C

Variant summary

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

The NM_032539.5(SLITRK2):​c.584T>C​(p.Val195Ala) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLITRK2 NM_032539.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

Genes affected

SLITRK2 (HGNC:13449): (SLIT and NTRK like family member 2) This gene encodes an integral membrane protein that contains two N-terminal leucine-rich repeats domains and contains C-terminal regions similar to neurotrophin receptors. The encoded protein may play a role in modulating neurite activity. Alternatively spliced transcript variants encoding the same protein have been described.[provided by RefSeq, Feb 2010]

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=0.17904562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5	c.584T>C	p.Val195Ala	missense_variant	Exon 5 of 5	ENST00000335565.6	NP_115928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK2	ENST00000335565.6	c.584T>C	p.Val195Ala	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5
SLITRK2	ENST00000370490.1	c.584T>C	p.Val195Ala	missense_variant	Exon 1 of 1	6		ENSP00000359521.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.584T>C (p.V195A) alteration is located in exon 5 (coding exon 1) of the SLITRK2 gene. This alteration results from a T to C substitution at nucleotide position 584, causing the valine (V) at amino acid position 195 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.085	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.036
Sift	Benign	0.23	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0090	B;B
Vest4		0.15
MutPred		0.40		Gain of catalytic residue at V195 (P = 0.0516);Gain of catalytic residue at V195 (P = 0.0516);
MVP		0.80
MPC		0.68
ClinPred		0.75	D
GERP RS		5.0
Varity_R		0.17
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-144904527;