Variant 3-51958159-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001174100.2(PCBP4):c.1114T>G(p.Ser372Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 1,612,922 control chromosomes in the GnomAD database, including 24 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 22 hom. )

Consequence

PCBP4
NM_001174100.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.640

Variant links:

Genes affected

PCBP4 (HGNC:8652): (poly(rC) binding protein 4) This gene encodes a member of the KH-domain protein subfamily. Proteins of this subfamily, also referred to as alpha-CPs, bind to RNA with a specificity for C-rich pyrimidine regions. Alpha-CPs play important roles in post-transcriptional activities and have different cellular distributions. This gene is induced by the p53 tumor suppressor, and the encoded protein can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G(2)-M. This gene's protein is found in the cytoplasm, yet it lacks the nuclear localization signals found in other subfamily members. Multiple alternatively spliced transcript variants have been described, but the full-length nature for only some has been determined. [provided by RefSeq, Jul 2008]

PCBP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063040853).

BP6

Variant 3-51958159-A-C is Benign according to our data. Variant chr3-51958159-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 784600.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCBP4	NM_001174100.2 linkuse as main transcript	c.1114T>G	p.Ser372Ala	missense_variant	14/14	ENST00000461554.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBP4	ENST00000461554.6 linkuse as main transcript	c.1114T>G	p.Ser372Ala	missense_variant	14/14	1	NM_001174100.2	P1	P57723-1

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

319

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000677

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00118

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:

0.00396

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00212

AC:

531

AN:

250220

Hom.:

AF XY:

0.00217

AC XY:

294

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00386

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00376

AC:

5494

AN:

1460772

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

2689

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.000778

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00463

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00210

AC:

319

AN:

152150

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000675

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00396

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.00224

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00217

AC:

264

EpiCase

AF:

0.00425

EpiControl

AF:

0.00386

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Benign

0.90

DEOGEN2

Benign

0.012

T;.;T;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.69

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0063

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

N;.;N;N;.

MutationTaster

Benign

0.99

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.45

N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.61

T;T;T;T;T

Sift4G

Benign

0.82

T;T;T;T;T

Polyphen

0.012

B;B;B;B;B

Vest4

0.13

MVP

0.30

MPC

0.36

ClinPred

0.0077

GERP RS

5.5

Varity_R

0.044

gMVP

0.18

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