Variant 21-45909438-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001384156.1(PCBP3):c.423T>C(p.Cys141Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,612,578 control chromosomes in the GnomAD database, including 425,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.78 ( 46927 hom., cov: 34)

Exomes 𝑓: 0.72 ( 378604 hom. )

Consequence

PCBP3
NM_001384156.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.128

Variant links:

Genes affected

PCBP3 (HGNC:8651): (poly(rC) binding protein 3) 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. The protein encoded by this gene lacks the nuclear localization signals found in other subfamily members. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

PCBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 21-45909438-T-C is Benign according to our data. Variant chr21-45909438-T-C is described in ClinVar as [Benign]. Clinvar id is 3059228.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.128 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBP3	NM_001384156.1 linkuse as main transcript	c.423T>C	p.Cys141Cys	synonymous_variant	10/18	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1 linkuse as main transcript	c.423T>C	p.Cys141Cys	synonymous_variant	10/18		NM_001384156.1	ENSP00000505796.1		P57721-1

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118059

AN:

152032

Hom.:

46878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.883

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.838

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.774

GnomAD3 exomes

AF:

0.767

AC:

191008

AN:

248872

Hom.:

74771

AF XY:

0.765

AC XY:

103303

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.930

Gnomad AMR exome

AF:

0.825

Gnomad ASJ exome

AF:

0.719

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.866

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.686

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.715

AC:

1044894

AN:

1460428

Hom.:

378604

Cov.:

AF XY:

0.719

AC XY:

522507

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.937

Gnomad4 AMR exome

AF:

0.819

Gnomad4 ASJ exome

AF:

0.719

Gnomad4 EAS exome

AF:

0.995

Gnomad4 SAS exome

AF:

0.862

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.777

AC:

118165

AN:

152150

Hom.:

46927

Cov.:

AF XY:

0.778

AC XY:

57837

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.924

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.995

Gnomad4 SAS

AF:

0.882

Gnomad4 FIN

AF:

0.685

Gnomad4 NFE

AF:

0.686

Gnomad4 OTH

AF:

0.776

Alfa

AF:

0.716

Hom.:

10491

Bravo

AF:

0.789

Asia WGS

AF:

0.949

AC:

3300

AN:

3478

EpiCase

AF:

0.690

EpiControl

AF:

0.695

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PCBP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 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

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.49

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