Variant chr22-43214105-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173050.5(SCUBE1):c.2038G>A(p.Val680Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000795 in 1,547,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

SCUBE1
NM_173050.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

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]

SCUBE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027972788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCUBE1	NM_173050.5 linkuse as main transcript	c.2038G>A	p.Val680Met	missense_variant	16/22	ENST00000360835.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCUBE1	ENST00000360835.9 linkuse as main transcript	c.2038G>A	p.Val680Met	missense_variant	16/22	1	NM_173050.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

148160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000679

Gnomad ASJ

AF:

0.00349

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

242902

Hom.:

AF XY:

0.000151

AC XY:

AN XY:

132296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00276

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000765

AC:

107

AN:

1399198

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

695284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.000230

GnomAD4 genome

AF:

0.000108

AC:

AN:

148160

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

72000

show subpopulations

Gnomad4 AFR

AF:

0.0000248

Gnomad4 AMR

AF:

0.0000679

Gnomad4 ASJ

AF:

0.00349

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000298

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.2038G>A (p.V680M) alteration is located in exon 16 (coding exon 16) of the SCUBE1 gene. This alteration results from a G to A substitution at nucleotide position 2038, causing the valine (V) at amino acid position 680 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.078

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.018

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.91

REVEL

Benign

0.086

Sift

Benign

0.12

Sift4G

Benign

0.38

Polyphen

0.17

Vest4

0.33

MVP

0.21

MPC

0.59

ClinPred

0.13

GERP RS

2.9

Varity_R

0.13

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over