Variant 11-70272383-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003626.5(PPFIA1):c.211G>A(p.Val71Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,613,868 control chromosomes in the GnomAD database, including 40,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3438 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37026 hom. )

Consequence

PPFIA1
NM_003626.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.66

Variant links:

Genes affected

PPFIA1 (HGNC:9245): (PTPRF interacting protein alpha 1) The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

PPFIA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001419276).

BP6

Variant 11-70272383-G-A is Benign according to our data. Variant chr11-70272383-G-A is described in ClinVar as [Benign]. Clinvar id is 3055877.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIA1	NM_003626.5 linkuse as main transcript	c.211G>A	p.Val71Ile	missense_variant	2/28	ENST00000253925.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA1	ENST00000253925.12 linkuse as main transcript	c.211G>A	p.Val71Ile	missense_variant	2/28	1	NM_003626.5	P1	Q13136-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31159

AN:

152070

Hom.:

3440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0876

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.218

AC:

54910

AN:

251416

Hom.:

6274

AF XY:

0.223

AC XY:

30343

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.0899

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.222

AC:

324875

AN:

1461680

Hom.:

37026

Cov.:

AF XY:

0.224

AC XY:

162844

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.205

AC:

31169

AN:

152188

Hom.:

3438

Cov.:

AF XY:

0.207

AC XY:

15414

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.0876

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.219

Hom.:

7483

Bravo

AF:

0.193

TwinsUK

AF:

0.228

AC:

846

ALSPAC

AF:

0.229

AC:

884

ESP6500AA

AF:

0.143

AC:

631

ESP6500EA

AF:

0.218

AC:

1874

ExAC

AF:

0.217

AC:

26366

Asia WGS

AF:

0.189

AC:

655

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPFIA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;.;.;T

Eigen

Benign

0.041

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;.;.

MutationTaster

Benign

0.000033

P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.38

N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.082

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.18

MPC

0.17

ClinPred

0.025

GERP RS

5.0

Varity_R

0.12

gMVP

0.59

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