Genetic Variant NM_032539.5:c.440G>A (chrX-145822865-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032539.5(SLITRK2):c.440G>A(p.Ser147Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,012 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5 link	c.440G>A	p.Ser147Asn	missense_variant	Exon 5 of 5	ENST00000335565.6	NP_115928.1	Q9H156-1B3KTY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK2	ENST00000335565.6 link	c.440G>A	p.Ser147Asn	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5		Q9H156-1B3KTY4
SLITRK2	ENST00000370490.1 link	c.440G>A	p.Ser147Asn	missense_variant	Exon 1 of 1	6		ENSP00000359521.1		Q9H156-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363368

show subpopulations

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

.;T

M_CAP

Pathogenic

0.39

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.23

Sift

Benign

0.035

D;D

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.53

MutPred

0.37

Gain of catalytic residue at S147 (P = 0.0545);Gain of catalytic residue at S147 (P = 0.0545);

MVP

0.82

MPC

1.4

ClinPred

0.87

GERP RS

5.2

Varity_R

0.50

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over