X-145822674-C-T

Variant names:

• chrX-145822674-C-T
• rs376893929
• NM_032539.5:c.249C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032539.5(SLITRK2):​c.249C>T​(p.Val83Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V83V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 21)
• Consequence: SLITRK2 NM_032539.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

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]

SLITRK2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked 111

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032539.5. 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
	SLITRK2	NM_032539.5	MANE Select	c.249C>T	p.Val83Val	synonymous	Exon 5 of 5	NP_115928.1	Q9H156-1
	SLITRK2	NM_001144003.3		c.249C>T	p.Val83Val	synonymous	Exon 5 of 5	NP_001137475.1	Q9H156-1
	SLITRK2	NM_001144004.3		c.249C>T	p.Val83Val	synonymous	Exon 5 of 5	NP_001137476.1	Q9H156-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK2	ENST00000335565.6	TSL:2 MANE Select	c.249C>T	p.Val83Val	synonymous	Exon 5 of 5	ENSP00000334374.5	Q9H156-1
	SLITRK2	ENST00000370490.1	TSL:6	c.249C>T	p.Val83Val	synonymous	Exon 1 of 1	ENSP00000359521.1	Q9H156-1
	SLITRK2	ENST00000867861.1		c.249C>T	p.Val83Val	synonymous	Exon 5 of 5	ENSP00000537920.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.9
DANN	Benign	0.86
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs376893929; hg19: chrX-144904192;