Genetic Variant NM_032539.5:c.55A>T (chrX-145822480-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_032539.5(SLITRK2):c.55A>T(p.Thr19Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T19A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.15

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked 111
Inheritance: XL Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

SLITRK2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.1956 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to intellectual developmental disorder, X-linked 111.

BP4

Computational evidence support a benign effect (MetaRNN=0.14347476).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLITRK2	NM_032539.5	MANE Select	c.55A>T	p.Thr19Ser	missense	Exon 5 of 5	NP_115928.1	Q9H156-1
SLITRK2	NM_001144003.3		c.55A>T	p.Thr19Ser	missense	Exon 5 of 5	NP_001137475.1	Q9H156-1
SLITRK2	NM_001144004.3		c.55A>T	p.Thr19Ser	missense	Exon 5 of 5	NP_001137476.1	Q9H156-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLITRK2	ENST00000335565.6	TSL:2 MANE Select	c.55A>T	p.Thr19Ser	missense	Exon 5 of 5	ENSP00000334374.5	Q9H156-1
SLITRK2	ENST00000370490.1	TSL:6	c.55A>T	p.Thr19Ser	missense	Exon 1 of 1	ENSP00000359521.1	Q9H156-1
SLITRK2	ENST00000867861.1		c.55A>T	p.Thr19Ser	missense	Exon 5 of 5	ENSP00000537920.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097759

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363117

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26395

American (AMR)

AF:

0.00

AC:

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19368

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

54100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841772

Other (OTH)

AF:

0.00

AC:

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.012

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.58

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

4.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.50

REVEL

Benign

0.078

Sift

Benign

0.52

Sift4G

Benign

0.88

Polyphen

0.22

Vest4

0.37

MutPred

0.33

Gain of disorder (P = 0.0566)

MVP

0.75

MPC

0.56

ClinPred

0.58

GERP RS

4.6

Varity_R

0.13

gMVP

0.34

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over