Genetic Variant PCBP3:p.Asp288Glu (chr21-45935260-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384156.1(PCBP3):c.864C>A(p.Asp288Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCBP3
NM_001384156.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.187

Publications

3 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20195568).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384156.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCBP3	NM_001384156.1	MANE Select	c.864C>A	p.Asp288Glu	missense	Exon 16 of 18	NP_001371085.1	P57721-1
PCBP3	NM_001348240.2		c.933C>A	p.Asp311Glu	missense	Exon 15 of 17	NP_001335169.1
PCBP3	NM_001382279.1		c.933C>A	p.Asp311Glu	missense	Exon 13 of 15	NP_001369208.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCBP3	ENST00000681687.1	MANE Select	c.864C>A	p.Asp288Glu	missense	Exon 16 of 18	ENSP00000505796.1	P57721-1
PCBP3	ENST00000400304.1	TSL:1	c.834C>A	p.Asp278Glu	missense	Exon 11 of 13	ENSP00000383159.1	E9PFP8
PCBP3	ENST00000400308.5	TSL:1	c.786C>A	p.Asp262Glu	missense	Exon 11 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248766

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459474

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5004

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110724

Other (OTH)

AF:

0.00

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.45

CADD

Benign

1.8

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.090

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.82

M_CAP

Benign

0.028

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.5

PhyloP100

0.19

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.0

REVEL

Benign

0.19

Sift

Benign

0.15

Sift4G

Benign

0.32

Polyphen

0.75

Vest4

0.74

MutPred

0.26

Gain of glycosylation at S290 (P = 0.1199)

MVP

0.31

MPC

0.49

ClinPred

0.066

GERP RS

-7.4

Varity_R

0.13

gMVP

0.77

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over