Variant 10-97002712-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000266058.9(SLIT1):c.4146T>A(p.His1382Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000844 in 1,421,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

SLIT1
ENST00000266058.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.378

Variant links:

Genes affected

SLIT1 (HGNC:11085): (slit guidance ligand 1) Enables Roundabout binding activity. Involved in axon extension involved in axon guidance; motor neuron axon guidance; and negative chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SLIT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039274156).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT1	NM_003061.3 linkuse as main transcript	c.4146T>A	p.His1382Gln	missense_variant	35/37	ENST00000266058.9	NP_003052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9 linkuse as main transcript	c.4146T>A	p.His1382Gln	missense_variant	35/37	1	NM_003061.3	ENSP00000266058	P1	O75093-1
SLIT1	ENST00000371070.8 linkuse as main transcript	c.4146T>A	p.His1382Gln	missense_variant	35/37	5		ENSP00000360109

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000178

AC:

AN:

224396

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

121164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000844

AC:

AN:

1421486

Hom.:

Cov.:

AF XY:

0.00000999

AC XY:

AN XY:

700984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000307

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.4146T>A (p.H1382Q) alteration is located in exon 35 (coding exon 35) of the SLIT1 gene. This alteration results from a T to A substitution at nucleotide position 4146, causing the histidine (H) at amino acid position 1382 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.6

DANN

Benign

0.73

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.7

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

0.42

N;N

REVEL

Benign

0.21

Sift

Benign

0.27

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.0

B;.

Vest4

0.21

MutPred

0.46

Loss of ubiquitination at K1385 (P = 0.0907);Loss of ubiquitination at K1385 (P = 0.0907);

MVP

0.43

MPC

0.44

ClinPred

0.047

GERP RS

-3.1

Varity_R

0.052

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over