5-169263608-A-G

Variant names:

• chr5-169263608-A-G
• rs62376934
• NM_003062.4:c.198-12149T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• Publications: 16 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	NM_003062.4	MANE Select	c.198-12149T>C		intron	N/A	NP_003053.2	O75094-1
	SLIT3	NM_001271946.2		c.198-12149T>C		intron	N/A	NP_001258875.2	O75094-4
	MIR585	NR_030311.1		n.87T>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLIT3	ENST00000519560.6	TSL:1 MANE Select	c.198-12149T>C		intron	N/A	ENSP00000430333.2	O75094-1
	SLIT3	ENST00000332966.8	TSL:1	c.198-12149T>C		intron	N/A	ENSP00000332164.8	O75094-4
	SLIT3	ENST00000518140.5	TSL:1	n.235-12149T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.759 AC: 113629 AN: 149728 Hom.: 44028 Cov.: 25

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

GnomAD2 exomes AF: 0.711 AC: 127758 AN: 179674 AF XY: 0.700

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 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.: 0 AF XY: 0.690 AC XY: 130498 AN XY: 189104

African (AFR) AF: 0.893 AC: 4963 AN: 5556

American (AMR) AF: 0.821 AC: 18168 AN: 22130

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 6608 AN: 9848

East Asian (EAS) AF: 0.884 AC: 7481 AN: 8464

South Asian (SAS) AF: 0.696 AC: 41637 AN: 59790

European-Finnish (FIN) AF: 0.740 AC: 22897 AN: 30922

Middle Eastern (MID) AF: 0.580 AC: 1486 AN: 2564

European-Non Finnish (NFE) AF: 0.654 AC: 112662 AN: 172290

Other (OTH) AF: 0.695 AC: 9908 AN: 14264

GnomAD4 genome AF: 0.759 AC: 113756 AN: 149848 Hom.: 44091 Cov.: 25 AF XY: 0.764 AC XY: 55925 AN XY: 73164

African (AFR) AF: 0.919 AC: 37578 AN: 40878

American (AMR) AF: 0.783 AC: 11877 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2369 AN: 3450

East Asian (EAS) AF: 0.891 AC: 4293 AN: 4818

South Asian (SAS) AF: 0.701 AC: 3305 AN: 4712

European-Finnish (FIN) AF: 0.742 AC: 7701 AN: 10380

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.659 AC: 44291 AN: 67160

Other (OTH) AF: 0.747 AC: 1559 AN: 2088

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.65
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62376934; hg19: chr5-168690612; COSMIC: COSV60615067;