Variant 3-51958125-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001174100.2(PCBP4):c.1148C>T(p.Thr383Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000774 in 1,608,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 1 hom. )

Consequence

PCBP4
NM_001174100.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90

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:

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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=0.25248492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBP4	NM_001174100.2 linkuse as main transcript	c.1148C>T	p.Thr383Ile	missense_variant	14/14	ENST00000461554.6	NP_001167571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCBP4	ENST00000461554.6 linkuse as main transcript	c.1148C>T	p.Thr383Ile	missense_variant	14/14	1	NM_001174100.2	ENSP00000417196	P1	P57723-1

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000277

AC:

AN:

245452

Hom.:

AF XY:

0.000249

AC XY:

AN XY:

132654

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000894

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000541

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000803

AC:

1169

AN:

1455844

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

554

AN XY:

724206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000993

Gnomad4 OTH exome

AF:

0.000948

GnomAD4 genome

AF:

0.000493

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000628

Hom.:

Bravo

AF:

0.000563

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000239

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

Sep 06, 2022

The c.1148C>T (p.T383I) alteration is located in exon 14 (coding exon 12) of the PCBP4 gene. This alteration results from a C to T substitution at nucleotide position 1148, causing the threonine (T) at amino acid position 383 to be replaced by an isoleucine (I). 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;.;T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

.;D;D;.;.

M_CAP

Benign

0.034

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

2.0

M;.;M;M;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.4

N;N;N;N;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.022

D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.47

MVP

0.64

MPC

1.3

ClinPred

0.13

GERP RS

5.5

Varity_R

0.14

gMVP

0.55

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