rs732594

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SCUBE3	NM_152753.4	c.829+758C>A		intron_variant		ENST00000274938.8	NP_689966.2
SCUBE3-AS1	XR_001744102.2	n.320+5572G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCUBE3	ENST00000274938.8	c.829+758C>A		intron_variant		1	NM_152753.4	ENSP00000274938	P1

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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.437

Alfa AF: 0.451 Hom.: 21812

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

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

Other links and lift over

dbSNP: rs732594; hg19: chr6-35206553;