21-45930793-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001384156.1(PCBP3):c.804G>A(p.Lys268=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: PCBP3 NM_001384156.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.93

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 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 criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCBP3	NM_001384156.1	c.804G>A	p.Lys268=	synonymous_variant	15/18	ENST00000681687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBP3	ENST00000681687.1	c.804G>A	p.Lys268=	synonymous_variant	15/18		NM_001384156.1	P4

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152266 Hom.: 0 Cov.: 34

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.: 1 AF XY: 0.00116 AC XY: 155 AN XY: 134180

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.: 6 Cov.: 18 AF XY: 0.00166 AC XY: 1031 AN XY: 620256

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.: 0 Cov.: 34 AF XY: 0.00109 AC XY: 81 AN XY: 74524

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.: 0

Bravo AF: 0.00144

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00290

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PCBP3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

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	12
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

Other links and lift over

dbSNP: rs148366893; hg19: chr21-47350707;