dbSNP rs141936653: SLIT3:p.Ala853Ala (chr5-168711055-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003062.4(SLIT3):c.2559G>A(p.Ala853Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,576,470 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 37 hom. )

Consequence

SLIT3
NM_003062.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.40

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-168711055-C-T is Benign according to our data. Variant chr5-168711055-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656055.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.4 with no splicing effect.

BS2

High AC in GnomAd4 at 526 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLIT3	NM_003062.4	MANE Select	c.2559G>A	p.Ala853Ala	synonymous	Exon 25 of 36	NP_003053.2	O75094-1
SLIT3	NM_001271946.2		c.2559G>A	p.Ala853Ala	synonymous	Exon 25 of 36	NP_001258875.2	O75094-4
SLIT3-AS2	NR_130737.1		n.698+855C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLIT3	ENST00000519560.6	TSL:1 MANE Select	c.2559G>A	p.Ala853Ala	synonymous	Exon 25 of 36	ENSP00000430333.2	O75094-1
SLIT3	ENST00000332966.8	TSL:1	c.2559G>A	p.Ala853Ala	synonymous	Exon 25 of 36	ENSP00000332164.8	O75094-4
SLIT3-AS2	ENST00000522615.1	TSL:2	n.2227+855C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

527

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0423

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00406

AC:

832

AN:

204902

AF XY:

0.00401

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000782

Gnomad FIN exome

AF:

0.0393

Gnomad NFE exome

AF:

0.000971

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00177

AC:

2515

AN:

1424192

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1231

AN XY:

705090

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

32254

American (AMR)

AF:

0.0000241

AC:

AN:

41544

Ashkenazi Jewish (ASJ)

AF:

0.0000800

AC:

AN:

24998

East Asian (EAS)

AF:

0.000533

AC:

AN:

37500

South Asian (SAS)

AF:

0.0000499

AC:

AN:

80188

European-Finnish (FIN)

AF:

0.0384

AC:

1992

AN:

51814

Middle Eastern (MID)

AF:

0.000705

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.000360

AC:

393

AN:

1091508

Other (OTH)

AF:

0.00162

AC:

AN:

58714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

130

259

389

518

648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00345

AC:

526

AN:

152278

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41560

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0423

AC:

449

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000926

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.000261

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.13

(source)

DANN

Benign

0.86

PhyloP100

-3.4

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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