dbSNP rs748566393: PPFIA2:p.Ala1097Ser (chr12-81277338-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003625.5(PPFIA2):c.3289G>T(p.Ala1097Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,568,584 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. 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. A1097T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PPFIA2
NM_003625.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

PPFIA2 (HGNC:9246): (PTPRF interacting protein alpha 2) 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. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein has been shown to bind the calcium/calmodulin-dependent serine protein kinase (MAGUK family) protein (also known as CASK) and proposed to regulate higher-order brain functions in mammals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

PPFIA2 links:

PPFIA2-AS1 (HGNC:53397): (PPFIA2 antisense RNA 1)

PPFIA2-AS1 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=0.113680154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA2	NM_003625.5 link	c.3289G>T	p.Ala1097Ser	missense_variant	Exon 28 of 33	ENST00000549396.6	NP_003616.2	O75334-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA2	ENST00000549396.6 link	c.3289G>T	p.Ala1097Ser	missense_variant	Exon 28 of 33	1	NM_003625.5	ENSP00000450337.1		O75334-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1416778

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701464

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:

0.00000368

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151806

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

.;.;T;.;.;.;T;.;.;.;.

Eigen

Benign

-0.067

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.56

T;T;T;T;T;T;T;T;T;.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.35

N;.;N;N;N;N;.;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.14

T;.;T;T;T;T;.;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;.;B;.;.;.;.;.;.;.;.

Vest4

0.26

MutPred

0.21

.;.;Gain of phosphorylation at A1097 (P = 0.0092);Gain of phosphorylation at A1097 (P = 0.0092);.;.;.;.;.;.;.;

MVP

0.42

MPC

1.1

ClinPred

0.90

GERP RS

6.0

Varity_R

0.081

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over