Variant chr10-97164836-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 4P and 7B. PP3_StrongBP6_ModerateBP7BS2

The NM_003061.3(SLIT1):c.252C>A(p.Leu84Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,613,462 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

SLIT1
NM_003061.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.643

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:

ARHGAP19-SLIT1 (HGNC:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ARHGAP19-SLIT1 links:

SLIT1 (HGNC:):

SLIT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

BayesDel_noAF computational evidence supports a deleterious effect, 0.56

BP6

Variant 10-97164836-G-T is Benign according to our data. Variant chr10-97164836-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640735.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.643 with no splicing effect.

BS2

High AC in GnomAd4 at 222 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT1	NM_003061.3 linkuse as main transcript	c.252C>A	p.Leu84Leu	synonymous_variant	2/37	ENST00000266058.9	NP_003052.2	O75093-1A6H8V1
ARHGAP19-SLIT1	NR_037909.1 linkuse as main transcript	n.1575C>A		non_coding_transcript_exon_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9 linkuse as main transcript	c.252C>A	p.Leu84Leu	synonymous_variant	2/37	1	NM_003061.3	ENSP00000266058.4		O75093-1
ARHGAP19-SLIT1	ENST00000479633.2 linkuse as main transcript	n.1529C>A		non_coding_transcript_exon_variant	12/15	2		ENSP00000473567.1

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00209

AC:

526

AN:

251390

Hom.:

AF XY:

0.00207

AC XY:

281

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00172

AC:

2509

AN:

1461238

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1255

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00157

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152224

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00312

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00284

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SLIT1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Pathogenic

0.56

CADD

Benign

6.8

DANN

Uncertain

0.98

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