rs10483081

Variant names:

• chr21-45714069-A-T
• rs10483081
• NM_001384156.1:c.-199-21323A>T

Variant summary

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

The NM_001384156.1(PCBP3):​c.-199-21323A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,140 control chromosomes in the GnomAD database, including 399 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 0.050 (399 hom., cov: 32)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.-199-21323A>T		intron_variant	Intron 2 of 17	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.-199-21323A>T		intron_variant	Intron 2 of 17		NM_001384156.1	ENSP00000505796.1
PCBP3	ENST00000400314.5	c.-163-21323A>T		intron_variant	Intron 1 of 15	5		ENSP00000383168.1
PCBP3	ENST00000465077.5	n.176-14607A>T		intron_variant	Intron 1 of 3	3
PCBP3	ENST00000594149.5	n.182-21323A>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7575 AN: 152022 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00529

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0499 AC: 7593 AN: 152140 Hom.: 399 Cov.: 32 AF XY: 0.0525 AC XY: 3907 AN XY: 74386

African (AFR) AF: 0.114 AC: 4713 AN: 41498

American (AMR) AF: 0.0787 AC: 1202 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.116 AC: 597 AN: 5168

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4822

European-Finnish (FIN) AF: 0.0262 AC: 278 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00527 AC: 358 AN: 67990

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0304 Hom.: 30

Bravo AF: 0.0582

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.24
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: rs10483081; hg19: chr21-47133983;