Variant 4-67558922-G-C 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_012108.4(STAP1):c.113G>C(p.Gly38Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

STAP1
NM_012108.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.431

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:

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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=0.058995217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAP1	NM_012108.4 linkuse as main transcript	c.113G>C	p.Gly38Ala	missense_variant	1/9	ENST00000265404.7	NP_036240.1	Q9ULZ2A0A024RD91
STAP1	NM_001317769.2 linkuse as main transcript	c.113G>C	p.Gly38Ala	missense_variant	1/10		NP_001304698.1	Q9ULZ2A0A024RD91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAP1	ENST00000265404.7 linkuse as main transcript	c.113G>C	p.Gly38Ala	missense_variant	1/9	1	NM_012108.4	ENSP00000265404.2		Q9ULZ2
STAP1	ENST00000396225.1 linkuse as main transcript	c.113G>C	p.Gly38Ala	missense_variant	1/10	1		ENSP00000379527.1		Q9ULZ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249178

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1459530

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 09, 2022

The p.G38A variant (also known as c.113G>C), located in coding exon 1 of the STAP1 gene, results from a G to C substitution at nucleotide position 113. The glycine at codon 38 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.58

.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.072

Sift

Benign

0.71

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.15

MutPred

0.23

Loss of glycosylation at S37 (P = 0.0479);Loss of glycosylation at S37 (P = 0.0479);

MVP

0.66

MPC

0.075

ClinPred

0.017

GERP RS

-0.19

Varity_R

0.036

gMVP

0.17

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

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