21-45914500-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384156.1(PCBP3):c.675+475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 216,964 control chromosomes in the GnomAD database, including 24,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (19136 hom., cov: 34)
  • Exomes 𝑓: 0.40 (5323 hom.)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0700

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-45914500-C-T is Benign according to our data. Variant chr21-45914500-C-T is described in ClinVar as [Benign]. Clinvar id is 3060839.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCBP3	NM_001384156.1	c.675+475C>T		intron_variant		ENST00000681687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBP3	ENST00000681687.1	c.675+475C>T		intron_variant			NM_001384156.1	P4
	ENST00000626237.1	n.205C>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71916 AN: 152050 Hom.: 19105 Cov.: 34

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.396 AC: 25627 AN: 64796 Hom.: 5323 Cov.: 0 AF XY: 0.394 AC XY: 12693 AN XY: 32184

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.473 AC: 71985 AN: 152168 Hom.: 19136 Cov.: 34 AF XY: 0.467 AC XY: 34713 AN XY: 74396

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.441

Alfa AF: 0.422 Hom.: 1909

Bravo AF: 0.491

Asia WGS AF: 0.377 AC: 1315 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PCBP3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 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	-0.92
Cadd	Benign	2.4
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs440207; hg19: chr21-47334414; COSMIC: COSV68407218;