Variant chr5-169263608-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003062.4(SLIT3):c.198-12149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 475,676 control chromosomes in the GnomAD database, including 123,387 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 44091 hom., cov: 25)

Exomes 𝑓: 0.69 ( 79296 hom. )

Consequence

SLIT3
NM_003062.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.783

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:

MIR585 (HGNC:32841): (microRNA 585) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR585 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SLIT3	NM_003062.4 linkuse as main transcript	c.198-12149T>C	intron_variant		ENST00000519560.6	NP_003053.2
MIR585	NR_030311.1 linkuse as main transcript	n.87T>C	non_coding_transcript_exon_variant	1/1
SLIT3	NM_001271946.2 linkuse as main transcript	c.198-12149T>C	intron_variant			NP_001258875.2
SLIT3	XM_017009779.1 linkuse as main transcript	c.8+9072T>C	intron_variant			XP_016865268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6 linkuse as main transcript	c.198-12149T>C		intron_variant		1	NM_003062.4	ENSP00000430333	A1	O75094-1
MIR585	ENST00000384887.1 linkuse as main transcript	n.87T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

113629

AN:

149728

Hom.:

44028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.701

Gnomad FIN

AF:

0.742

Gnomad MID

AF:

0.647

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.711

AC:

127758

AN:

179674

Hom.:

46165

AF XY:

0.700

AC XY:

69949

AN XY:

99912

show subpopulations

Gnomad AFR exome

AF:

0.913

Gnomad AMR exome

AF:

0.822

Gnomad ASJ exome

AF:

0.671

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.688

Gnomad FIN exome

AF:

0.736

Gnomad NFE exome

AF:

0.641

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.693

AC:

225810

AN:

325828

Hom.:

79296

Cov.:

AF XY:

0.690

AC XY:

130498

AN XY:

189104

show subpopulations

Gnomad4 AFR exome

AF:

0.893

Gnomad4 AMR exome

AF:

0.821

Gnomad4 ASJ exome

AF:

0.671

Gnomad4 EAS exome

AF:

0.884

Gnomad4 SAS exome

AF:

0.696

Gnomad4 FIN exome

AF:

0.740

Gnomad4 NFE exome

AF:

0.654

Gnomad4 OTH exome

AF:

0.695

GnomAD4 genome

AF:

0.759

AC:

113756

AN:

149848

Hom.:

44091

Cov.:

AF XY:

0.764

AC XY:

55925

AN XY:

73164

show subpopulations

Gnomad4 AFR

AF:

0.919

Gnomad4 AMR

AF:

0.783

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.891

Gnomad4 SAS

AF:

0.701

Gnomad4 FIN

AF:

0.742

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.747

Alfa

AF:

0.701

Hom.:

16456

Bravo

AF:

0.769

Asia WGS

AF:

0.798

AC:

2775

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.57

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over