21-45889679-T-C

Variant names:

• chr21-45889679-T-C
• rs2839036
• NM_001384156.1:c.11-6529T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384156.1(PCBP3):​c.11-6529T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,040 control chromosomes in the GnomAD database, including 19,979 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19979 hom., cov: 33)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.11-6529T>C		intron_variant	Intron 5 of 17	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.11-6529T>C		intron_variant	Intron 5 of 17		NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74066 AN: 151922 Hom.: 19937 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74149 AN: 152040 Hom.: 19979 Cov.: 33 AF XY: 0.484 AC XY: 35938 AN XY: 74320

African (AFR) AF: 0.729 AC: 30244 AN: 41482

American (AMR) AF: 0.414 AC: 6325 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1616 AN: 5142

South Asian (SAS) AF: 0.407 AC: 1955 AN: 4806

European-Finnish (FIN) AF: 0.365 AC: 3865 AN: 10590

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27140 AN: 67940

Other (OTH) AF: 0.456 AC: 965 AN: 2116

Alfa AF: 0.420 Hom.: 1792

Bravo AF: 0.503

Asia WGS AF: 0.393 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.38
PhyloP100		-2.6
Mutation Taster		=100/0	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: rs2839036; hg19: chr21-47309593;