dbSNP rs758633713: VASP:p.Pro135Thr (chr19-45521381-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003370.4(VASP):c.403C>A(p.Pro135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P135A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VASP
NM_003370.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.688

Publications

0 publications found

Variant links:

Genes affected

VASP (HGNC:12652): (vasodilator stimulated phosphoprotein) Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an EHV1 N-terminal domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions. In the mid-region of the protein, family members have a proline-rich domain that binds SH3 and WW domain-containing proteins. Their C-terminal EVH2 domain mediates tetramerization and binds both G and F actin. VASP is associated with filamentous actin formation and likely plays a widespread role in cell adhesion and motility. VASP may also be involved in the intracellular signaling pathways that regulate integrin-extracellular matrix interactions. VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. [provided by RefSeq, Jul 2008]

VASP links:

LOC107985315 (HGNC:):

LOC107985315 links:

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ACMG classification

Classification was made for transcript

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=0.09570995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003370.4. 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
	VASP	NM_003370.4	MANE Select	c.403C>A	p.Pro135Thr	missense	Exon 4 of 13	NP_003361.1	A0A024R0V4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VASP	ENST00000245932.11	TSL:1 MANE Select	c.403C>A	p.Pro135Thr	missense	Exon 4 of 13	ENSP00000245932.5	P50552
VASP	ENST00000916562.1		c.496C>A	p.Pro166Thr	missense	Exon 4 of 13	ENSP00000586621.1
VASP	ENST00000862928.1		c.403C>A	p.Pro135Thr	missense	Exon 4 of 13	ENSP00000532987.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000531

AC:

AN:

188446

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1423942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705168

African (AFR)

AF:

0.00

AC:

AN:

32836

American (AMR)

AF:

0.00

AC:

AN:

38626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

38126

South Asian (SAS)

AF:

0.00

AC:

AN:

81196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5146

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093024

Other (OTH)

AF:

0.00

AC:

AN:

58846

GnomAD4 genome

Cov.:

Alfa

AF:

0.000291

Hom.:

ExAC

AF:

0.0000251

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.71

M_CAP

Benign

0.013

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.69

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.11

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.0010

Vest4

0.21

MutPred

0.14

Gain of phosphorylation at P135 (P = 0.0213)

MVP

0.46

MPC

0.38

ClinPred

0.22

GERP RS

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.093

gMVP

0.28

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over