Variant chr1-203056486-C-G 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_001304331.2(PPFIA4):c.2218C>G(p.Leu740Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PPFIA4
NM_001304331.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.416

Variant links:

Genes affected

PPFIA4 (HGNC:9248): (PTPRF interacting protein alpha 4) PPFIA4, or liprin-alpha-4, belongs to the liprin-alpha gene family. See liprin-alpha-1 (LIP1, or PPFIA1; MIM 611054) for background on liprins.[supplied by OMIM, Mar 2008]

PPFIA4 links:

PPFIA4 (HGNC:):

PPFIA4 links:

Genome browser will be placed here

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=0.03579867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPFIA4	NM_001304331.2 linkuse as main transcript	c.2218C>G	p.Leu740Val	missense_variant	18/30	ENST00000295706.9	NP_001291260.1	O75335A0A8J8YUZ5B4DIS5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIA4	ENST00000295706.9 linkuse as main transcript	c.2218C>G	p.Leu740Val	missense_variant	18/30	5	NM_001304331.2	ENSP00000295706.5		A0A8J8YUZ5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727060

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000907

ExAC

AF:

0.00000827

AC:

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

Nov 28, 2023

The c.700C>G (p.L234V) alteration is located in exon 5 (coding exon 5) of the PPFIA4 gene. This alteration results from a C to G substitution at nucleotide position 700, causing the leucine (L) at amino acid position 234 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0049

T;.;T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.91

D;D;D;D;.

M_CAP

Benign

0.0074

MetaRNN

Benign

0.036

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;.;L;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.53

N;N;N;N;.

REVEL

Benign

0.046

Sift

Benign

0.38

T;T;T;T;.

Sift4G

Benign

0.48

T;T;T;T;T

Polyphen

0.70

.;P;.;.;P

Vest4

0.25

MutPred

0.14

.;Gain of methylation at K237 (P = 0.1947);.;Gain of methylation at K237 (P = 0.1947);Gain of methylation at K237 (P = 0.1947);

MVP

0.29

MPC

0.46

ClinPred

0.095

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.30

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

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