Genetic Variant PCBP3:p.Val191Leu (chr21-45911001-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001384156.1(PCBP3):c.571G>C(p.Val191Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V191I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PCBP3
NM_001384156.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.53

Publications

0 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39068633).

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.571G>C	p.Val191Leu	missense	Exon 11 of 18	NP_001371085.1	P57721-1
PCBP3	NM_001348240.2		c.571G>C	p.Val191Leu	missense	Exon 10 of 17	NP_001335169.1
PCBP3	NM_001382279.1		c.571G>C	p.Val191Leu	missense	Exon 8 of 15	NP_001369208.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCBP3	ENST00000681687.1	MANE Select	c.571G>C	p.Val191Leu	missense	Exon 11 of 18	ENSP00000505796.1	P57721-1
PCBP3	ENST00000400304.1	TSL:1	c.475G>C	p.Val159Leu	missense	Exon 6 of 13	ENSP00000383159.1	E9PFP8
PCBP3	ENST00000400308.5	TSL:1	c.571G>C	p.Val191Leu	missense	Exon 7 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459378

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111940

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.012

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.70

PhyloP100

9.5

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-2.1

REVEL

Benign

0.23

Sift

Uncertain

0.0040

Sift4G

Benign

0.096

Polyphen

0.010

Vest4

0.72

MutPred

0.50

Gain of catalytic residue at V191 (P = 0.0044)

MVP

0.30

MPC

0.86

ClinPred

0.76

GERP RS

5.7

Varity_R

0.45

gMVP

0.85

Mutation Taster

=52/48

polymorphism

(source)

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

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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