rs732594

Variant names:

• chr6-35238776-C-A
• rs732594
• NM_152753.4:c.829+758C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-35238776-C-A
• chr6-35238776-C-G

Variant summary

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

The NM_152753.4(SCUBE3):​c.829+758C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,922 control chromosomes in the GnomAD database, including 16,266 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 0.46 (16266 hom., cov: 31)
• Consequence: SCUBE3 NM_152753.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 20 publications found

Genes affected

SCUBE3 (HGNC:13655): (signal peptide, CUB domain and EGF like domain containing 3) This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

SCUBE3-AS1 (HGNC:56671): (SCUBE3 antisense RNA 1)

ENSG00000305352 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE3	NM_152753.4	c.829+758C>A		intron_variant	Intron 7 of 21	ENST00000274938.8	NP_689966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE3	ENST00000274938.8	c.829+758C>A		intron_variant	Intron 7 of 21	1	NM_152753.4	ENSP00000274938.7
ENSG00000305352	ENST00000810546.1	n.261+5572G>T		intron_variant	Intron 2 of 2
ENSG00000305352	ENST00000810547.1	n.456+5572G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69989 AN: 151802 Hom.: 16230 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.461 AC: 70062 AN: 151922 Hom.: 16266 Cov.: 31 AF XY: 0.462 AC XY: 34274 AN XY: 74226

African (AFR) AF: 0.445 AC: 18441 AN: 41412

American (AMR) AF: 0.522 AC: 7973 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1164 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1864 AN: 5158

South Asian (SAS) AF: 0.532 AC: 2554 AN: 4804

European-Finnish (FIN) AF: 0.479 AC: 5058 AN: 10558

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31432 AN: 67936

Other (OTH) AF: 0.437 AC: 923 AN: 2110

Alfa AF: 0.453 Hom.: 31516

Bravo AF: 0.462

Asia WGS AF: 0.441 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.76
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: rs732594; hg19: chr6-35206553;