Genetic Variant SLIT3:c.2719+9C>T (chr5-168710886-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003062.4(SLIT3):c.2719+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,513,874 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

SLIT3
NM_003062.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.532

Variant links:

Genes affected

SLIT3 (HGNC:11087): (slit guidance ligand 3) The protein encoded by this gene is secreted, likely interacting with roundabout homolog receptors to effect cell migration. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

SLIT3 links:

SLIT3-AS2 (HGNC:40551): (SLIT3 antisense RNA 2)

SLIT3-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-168710886-G-A is Benign according to our data. Variant chr5-168710886-G-A is described in ClinVar as [Benign]. Clinvar id is 723995.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 272 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4 link	c.2719+9C>T	intron_variant	Intron 25 of 35	ENST00000519560.6	NP_003053.2	O75094-1
SLIT3	NM_001271946.2 link	c.2719+9C>T	intron_variant	Intron 25 of 35		NP_001258875.2	O75094-4
SLIT3	XM_017009779.1 link	c.2530+9C>T	intron_variant	Intron 25 of 35		XP_016865268.1
SLIT3-AS2	NR_130737.1 link	n.698+686G>A	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLIT3	ENST00000519560.6 link	c.2719+9C>T	intron_variant	Intron 25 of 35	1	NM_003062.4	ENSP00000430333.2	O75094-1
SLIT3	ENST00000332966.8 link	c.2719+9C>T	intron_variant	Intron 25 of 35	1		ENSP00000332164.8	O75094-4
SLIT3-AS2	ENST00000522615.1 link	n.2227+686G>A	intron_variant	Intron 2 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000469

AC:

AN:

142934

Hom.:

AF XY:

0.000347

AC XY:

AN XY:

74928

show subpopulations

Gnomad AFR exome

AF:

0.00679

Gnomad AMR exome

AF:

0.000143

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000176

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:

0.000214

AC:

292

AN:

1361574

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

135

AN XY:

666760

show subpopulations

Gnomad4 AFR exome

AF:

0.00713

Gnomad4 AMR exome

AF:

0.000276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.0000407

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000265

Gnomad4 OTH exome

AF:

0.000445

GnomAD4 genome

AF:

0.00179

AC:

272

AN:

152300

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00630

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00219

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.9

DANN

Benign

0.75

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