X-145822499-C-G

Variant names:

• chrX-145822499-C-G
• NM_032539.5:c.74C>G

Variant summary

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

The NM_032539.5(SLITRK2):​c.74C>G​(p.Ala25Gly) 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. 13/20 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: 22)
• Consequence: SLITRK2 NM_032539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

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=0.16778612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5	c.74C>G	p.Ala25Gly	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.74C>G	p.Ala25Gly	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5
SLITRK2	ENST00000370490.1	c.74C>G	p.Ala25Gly	missense_variant	Exon 1 of 1	6		ENSP00000359521.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.081
Sift	Benign	0.32	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0	B;B
Vest4		0.085
MutPred		0.34		Gain of ubiquitination at K23 (P = 0.0685);Gain of ubiquitination at K23 (P = 0.0685);
MVP		0.74
MPC		0.54
ClinPred		0.43	T
GERP RS		3.8
Varity_R		0.27
gMVP		0.39

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-144904017;