21-45896212-C-T

Variant names:

• chr21-45896212-C-T
• rs113211675
• NM_001384156.1:c.15C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001348242.2(PCBP3):​c.-82C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,551,550 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (11 hom., cov: 34)
  • Exomes 𝑓: 0.00087 (6 hom.)
• Consequence: PCBP3 NM_001348242.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.08

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 Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 21-45896212-C-T is Benign according to our data. Variant chr21-45896212-C-T is described in ClinVar as [Benign]. Clinvar id is 712872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0057 (868/152398) while in subpopulation AFR AF= 0.0185 (770/41600). AF 95% confidence interval is 0.0174. There are 11 homozygotes in gnomad4. There are 419 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.15C>T	p.Asp5Asp	synonymous_variant	Exon 6 of 18	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.15C>T	p.Asp5Asp	synonymous_variant	Exon 6 of 18		NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.00567 AC: 863 AN: 152280 Hom.: 11 Cov.: 34

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00955

GnomAD3 exomes AF: 0.00174 AC: 275 AN: 158454 Hom.: 2 AF XY: 0.00148 AC XY: 123 AN XY: 83386

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000210

Gnomad OTH exome AF: 0.000446

GnomAD4 exome AF: 0.000866 AC: 1211 AN: 1399152 Hom.: 6 Cov.: 32 AF XY: 0.000809 AC XY: 558 AN XY: 690092

Gnomad4 AFR exome AF: 0.0214

Gnomad4 AMR exome AF: 0.00120

Gnomad4 ASJ exome AF: 0.00489

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000199

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152398 Hom.: 11 Cov.: 34 AF XY: 0.00562 AC XY: 419 AN XY: 74524

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00304 Hom.: 1

Bravo AF: 0.00674

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PCBP3-related disorder Benign:1

Jan 02, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.27
CADD	Benign	14
DANN	Benign	0.71

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: rs113211675; hg19: chr21-47316126;