rs374163921

Variant names:

• chrX-145822960-C-A
• NM_032539.5:c.535C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-145822960-C-A
• chrX-145822960-C-G
• chrX-145822960-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032539.5(SLITRK2):​c.535C>A​(p.Arg179Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,004 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SLITRK2 NM_032539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5	c.535C>A	p.Arg179Ser	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.535C>A	p.Arg179Ser	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5
SLITRK2	ENST00000370490.1	c.535C>A	p.Arg179Ser	missense_variant	Exon 1 of 1	6		ENSP00000359521.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098004 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363360

Gnomad4 AFR exome AF: 0.00

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.47	N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.74
MutPred		0.64		Loss of methylation at R179 (P = 0.0257);Loss of methylation at R179 (P = 0.0257);
MVP		0.72
MPC		1.5
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.90
gMVP		0.84

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-144904478;