NM_001384156.1:c.423T>C

Variant names:

• chr21-45909438-T-C
• rs2277812
• NM_001384156.1:c.423T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001384156.1(PCBP3):​c.423T>C​(p.Cys141Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,612,578 control chromosomes in the GnomAD database, including 425,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.78 (46927 hom., cov: 34)
  • Exomes 𝑓: 0.72 (378604 hom.)
• Consequence: PCBP3 NM_001384156.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.128
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-45909438-T-C is Benign according to our data. Variant chr21-45909438-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059228.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.128 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	NM_001384156.1	MANE Select	c.423T>C	p.Cys141Cys	synonymous	Exon 10 of 18	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.423T>C	p.Cys141Cys	synonymous	Exon 9 of 17	NP_001335169.1
	PCBP3	NM_001382279.1		c.423T>C	p.Cys141Cys	synonymous	Exon 7 of 15	NP_001369208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.423T>C	p.Cys141Cys	synonymous	Exon 10 of 18	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.327T>C	p.Cys109Cys	synonymous	Exon 5 of 13	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.423T>C	p.Cys141Cys	synonymous	Exon 6 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118059 AN: 152032 Hom.: 46878 Cov.: 34

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.767 AC: 191008 AN: 248872 AF XY: 0.765

Gnomad AFR exome AF: 0.930

Gnomad AMR exome AF: 0.825

Gnomad ASJ exome AF: 0.719

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.680

Gnomad NFE exome AF: 0.686

Gnomad OTH exome AF: 0.750

GnomAD4 exome AF: 0.715 AC: 1044894 AN: 1460428 Hom.: 378604 Cov.: 43 AF XY: 0.719 AC XY: 522507 AN XY: 726538

African (AFR) AF: 0.937 AC: 31362 AN: 33472

American (AMR) AF: 0.819 AC: 36614 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 18779 AN: 26106

East Asian (EAS) AF: 0.995 AC: 39499 AN: 39690

South Asian (SAS) AF: 0.862 AC: 74336 AN: 86244

European-Finnish (FIN) AF: 0.683 AC: 36097 AN: 52862

Middle Eastern (MID) AF: 0.824 AC: 4747 AN: 5760

European-Non Finnish (NFE) AF: 0.682 AC: 758355 AN: 1111262

Other (OTH) AF: 0.748 AC: 45105 AN: 60334

GnomAD4 genome AF: 0.777 AC: 118165 AN: 152150 Hom.: 46927 Cov.: 34 AF XY: 0.778 AC XY: 57837 AN XY: 74384

African (AFR) AF: 0.924 AC: 38371 AN: 41522

American (AMR) AF: 0.759 AC: 11611 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5146 AN: 5172

South Asian (SAS) AF: 0.882 AC: 4254 AN: 4824

European-Finnish (FIN) AF: 0.685 AC: 7252 AN: 10592

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.686 AC: 46612 AN: 67954

Other (OTH) AF: 0.776 AC: 1638 AN: 2110

Alfa AF: 0.722 Hom.: 22682

Bravo AF: 0.789

Asia WGS AF: 0.949 AC: 3300 AN: 3478

EpiCase AF: 0.690

EpiControl AF: 0.695

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PCBP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		-0.13
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2277812; hg19: chr21-47329352; COSMIC: COSV68407953; COSMIC: COSV68407953;