chr22-43210151-C-T

Variant names:

• chr22-43210151-C-T
• rs145262250
• NM_173050.5:c.2473G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173050.5(SCUBE1):​c.2473G>A​(p.Val825Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SCUBE1 NM_173050.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

Genes affected

SCUBE1 (HGNC:13441): (signal peptide, CUB domain and EGF like domain containing 1) This gene encodes a cell surface glycoprotein that is a member of the SCUBE (signal peptide, CUB domain, EGF (epidermal growth factor)-like protein) family. Family members have an amino-terminal signal peptide, nine copies of EGF-like repeats and a CUB domain at the carboxyl terminus. This protein is expressed in platelets and endothelial cells and may play an important role in vascular biology. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17479613).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173050.5. 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
	SCUBE1	NM_173050.5	MANE Select	c.2473G>A	p.Val825Ile	missense	Exon 19 of 22	NP_766638.2	Q8IWY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE1	ENST00000360835.9	TSL:1 MANE Select	c.2473G>A	p.Val825Ile	missense	Exon 19 of 22	ENSP00000354080.3	Q8IWY4
	SCUBE1	ENST00000911327.1		c.2410G>A	p.Val804Ile	missense	Exon 19 of 22	ENSP00000581386.1
	SCUBE1	ENST00000911329.1		c.2410G>A	p.Val804Ile	missense	Exon 19 of 22	ENSP00000581388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247564 AF XY: 0.00

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1458656 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 725588

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 85982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110816

Other (OTH) AF: 0.0000332 AC: 2 AN: 60274

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.050	N
PhyloP100		2.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.13
Sift	Benign	0.47	T
Sift4G	Benign	0.48	T
Polyphen		0.0070	B
Vest4		0.26
MVP		0.16
MPC		0.55
ClinPred		0.074	T
GERP RS		2.5
Varity_R		0.032
gMVP		0.12
Mutation Taster		=84/16	polymorphism

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: rs145262250; hg19: chr22-43606157; COSMIC: COSV62615668; COSMIC: COSV62615668;