Variant 4-67558877-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012108.4(STAP1):c.68C>T(p.Ala23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,846 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

STAP1
NM_012108.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

STAP1 (HGNC:24133): (signal transducing adaptor family member 1) The protein encoded by this gene contains a proline-rich region, a pleckstrin homology (PH) domain, and a region in the carboxy terminal half with similarity to the Src Homology 2 (SH2) domain. This protein is a substrate of tyrosine-protein kinase Tec, and its interaction with tyrosine-protein kinase Tec is phosphorylation-dependent. This protein is thought to participate in a positive feedback loop by upregulating the activity of tyrosine-protein kinase Tec. Variants of this gene have been associated with autosomal-dominant hypercholesterolemia (ADH), which is characterized by elevated low-density lipoprotein cholesterol levels and in increased risk of coronary vascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

STAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078356385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAP1	NM_012108.4 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	1/9	ENST00000265404.7
STAP1	NM_001317769.2 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAP1	ENST00000265404.7 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	1/9	1	NM_012108.4	P1
STAP1	ENST00000396225.1 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	1/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000876

AC:

AN:

251242

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000223

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000954

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.042

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.30

B;B

Vest4

0.50

MVP

0.32

MPC

0.10

ClinPred

0.022

GERP RS

5.4

Varity_R

0.13

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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