Genetic Variant PCBP3:p.Lys268Lys (chr21-45930793-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001384156.1(PCBP3):c.804G>A(p.Lys268Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00162 in 1,372,870 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

PCBP3
NM_001384156.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.93

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 21-45930793-G-A is Benign according to our data. Variant chr21-45930793-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050353.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1 link	c.804G>A	p.Lys268Lys	synonymous_variant	Exon 15 of 18	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1 link	c.804G>A	p.Lys268Lys	synonymous_variant	Exon 15 of 18		NM_001384156.1	ENSP00000505796.1		P57721-1

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

200

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00107

AC:

265

AN:

246696

Hom.:

AF XY:

0.00116

AC XY:

155

AN XY:

134180

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00182

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00166

AC:

2023

AN:

1220486

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1031

AN XY:

620256

show subpopulations

Gnomad4 AFR exome

AF:

0.000276

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.0000404

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000184

Gnomad4 FIN exome

AF:

0.0000945

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00131

AC:

200

AN:

152384

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00144

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00290

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PCBP3-related disorder

Benign:1

Nov 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

-0.37

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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