rs62376935

Variant names:

• chr5-169263631-C-T
• rs62376935
• NM_003062.4:c.198-12172G>A

Variant summary

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

The NM_003062.4(SLIT3):​c.198-12172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 495,762 control chromosomes in the GnomAD database, including 1,948 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 0.061 (438 hom., cov: 27)
  • Exomes 𝑓: 0.076 (1510 hom.)
• Consequence: SLIT3 NM_003062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 18 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLIT3	NM_003062.4	c.198-12172G>A		intron_variant	Intron 1 of 35	ENST00000519560.6	NP_003053.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLIT3	ENST00000519560.6	c.198-12172G>A		intron_variant	Intron 1 of 35	1	NM_003062.4	ENSP00000430333.2

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9131 AN: 150516 Hom.: 441 Cov.: 27

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0647

GnomAD2 exomes AF: 0.0812 AC: 16719 AN: 205798 AF XY: 0.0833

Gnomad AFR exome AF: 0.0339

Gnomad AMR exome AF: 0.0368

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0679

Gnomad OTH exome AF: 0.0822

GnomAD4 exome AF: 0.0761 AC: 26259 AN: 345128 Hom.: 1510 Cov.: 0 AF XY: 0.0795 AC XY: 15849 AN XY: 199478

African (AFR) AF: 0.0388 AC: 259 AN: 6682

American (AMR) AF: 0.0368 AC: 985 AN: 26744

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 576 AN: 10486

East Asian (EAS) AF: 0.306 AC: 2884 AN: 9418

South Asian (SAS) AF: 0.105 AC: 6571 AN: 62540

European-Finnish (FIN) AF: 0.0537 AC: 1709 AN: 31816

Middle Eastern (MID) AF: 0.0668 AC: 182 AN: 2724

European-Non Finnish (NFE) AF: 0.0662 AC: 11897 AN: 179652

Other (OTH) AF: 0.0794 AC: 1196 AN: 15066

GnomAD4 genome AF: 0.0606 AC: 9128 AN: 150634 Hom.: 438 Cov.: 27 AF XY: 0.0630 AC XY: 4633 AN XY: 73526

African (AFR) AF: 0.0307 AC: 1263 AN: 41140

American (AMR) AF: 0.0533 AC: 811 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 191 AN: 3456

East Asian (EAS) AF: 0.262 AC: 1267 AN: 4838

South Asian (SAS) AF: 0.105 AC: 495 AN: 4732

European-Finnish (FIN) AF: 0.0463 AC: 485 AN: 10482

Middle Eastern (MID) AF: 0.0759 AC: 22 AN: 290

European-Non Finnish (NFE) AF: 0.0654 AC: 4413 AN: 67474

Other (OTH) AF: 0.0645 AC: 135 AN: 2094

Alfa AF: 0.0600 Hom.: 162

Bravo AF: 0.0585

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.28
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: rs62376935; hg19: chr5-168690635; COSMIC: COSV60607362;