Genetic Variant NM_003062.4:c.2643C>T (chr5-168710971-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003062.4(SLIT3):c.2643C>T(p.Ile881Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,566,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SLIT3
NM_003062.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.587

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 5-168710971-G-A is Benign according to our data. Variant chr5-168710971-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2498992.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.587 with no splicing effect.

BS2

High AC in GnomAd4 at 8 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.2643C>T	p.Ile881Ile	synonymous	Exon 25 of 36	NP_003053.2	O75094-1
SLIT3	NM_001271946.2		c.2643C>T	p.Ile881Ile	synonymous	Exon 25 of 36	NP_001258875.2	O75094-4
SLIT3-AS2	NR_130737.1		n.698+771G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLIT3	ENST00000519560.6	TSL:1 MANE Select	c.2643C>T	p.Ile881Ile	synonymous	Exon 25 of 36	ENSP00000430333.2	O75094-1
SLIT3	ENST00000332966.8	TSL:1	c.2643C>T	p.Ile881Ile	synonymous	Exon 25 of 36	ENSP00000332164.8	O75094-4
SLIT3-AS2	ENST00000522615.1	TSL:2	n.2227+771G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000285

AC:

AN:

175632

AF XY:

0.0000430

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.0000378

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1414760

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

699016

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

32624

American (AMR)

AF:

0.0000265

AC:

AN:

37770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25232

East Asian (EAS)

AF:

0.00

AC:

AN:

37436

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000166

AC:

AN:

1086960

Other (OTH)

AF:

0.000102

AC:

AN:

58686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000658

Hom.:

Bravo

AF:

0.0000378

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

-0.46

CADD

Benign

1.3

(source)

DANN

Benign

0.88

PhyloP100

-0.59

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

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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