Genetic Variant SLITRK5:p.Gln118His (chr13-87675742-G-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001384609.1(SLITRK5):c.354G>T(p.Gln118His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,614,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

SLITRK5
NM_001384609.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.825

Publications

2 publications found

Variant links:

Genes affected

SLITRK5 (HGNC:20295): (SLIT and NTRK like family member 5) Members of the SLITRK family, such as SLITRK5, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1; MIM 603742). Most SLITRKs, including SLITRK5, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1; MIM 191315). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity (Aruga et al., 2003 [PubMed 14557068]).[supplied by OMIM, Mar 2008]

SLITRK5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0082785785).

BP6

Variant 13-87675742-G-T is Benign according to our data. Variant chr13-87675742-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3040238.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384609.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLITRK5	NM_001384609.1	MANE Select	c.354G>T	p.Gln118His	missense	Exon 2 of 2	NP_001371538.1	O94991-1
SLITRK5	NM_001384610.1		c.354G>T	p.Gln118His	missense	Exon 2 of 2	NP_001371539.1	O94991-1
SLITRK5	NM_015567.2		c.354G>T	p.Gln118His	missense	Exon 2 of 2	NP_056382.1	O94991-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLITRK5	ENST00000683689.1	MANE Select	c.354G>T	p.Gln118His	missense	Exon 2 of 2	ENSP00000508338.1	O94991-1
SLITRK5	ENST00000325089.7	TSL:1	c.354G>T	p.Gln118His	missense	Exon 2 of 2	ENSP00000366283.2	O94991-1
SLITRK5	ENST00000933099.1		c.354G>T	p.Gln118His	missense	Exon 3 of 3	ENSP00000603158.1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00618

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000445

AC:

112

AN:

251472

AF XY:

0.000464

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00571

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000166

AC:

242

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00514

AC:

204

AN:

39700

South Asian (SAS)

AF:

0.000220

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111994

Other (OTH)

AF:

0.000265

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000243

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41538

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00619

AC:

AN:

5168

South Asian (SAS)

AF:

0.000831

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000355

Hom.:

Bravo

AF:

0.000351

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLITRK5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

M_CAP

Benign

0.013

MetaRNN

Benign

0.0083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

0.82

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.070

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.14

Vest4

0.39

MutPred

0.27

Loss of stability (P = 0.146)

MVP

0.16

MPC

0.42

ClinPred

0.088

GERP RS

4.1

Varity_R

0.32

gMVP

0.55

Mutation Taster

=87/13

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over