21-45860087-A-G

Variant names:

• chr21-45860087-A-G
• rs2839020
• NM_001384156.1:c.10+9992A>G

Variant summary

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

The NM_001384156.1(PCBP3):​c.10+9992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,944 control chromosomes in the GnomAD database, including 46,742 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 0.78 (46742 hom., cov: 30)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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]

LOC124905044 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	NM_001384156.1	MANE Select	c.10+9992A>G		intron	N/A	NP_001371085.1
	PCBP3	NM_001348240.2		c.10+9992A>G		intron	N/A	NP_001335169.1
	PCBP3	NM_001382279.1		c.10+9992A>G		intron	N/A	NP_001369208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.10+9992A>G		intron	N/A	ENSP00000505796.1
	PCBP3	ENST00000400308.5	TSL:1	c.10+9992A>G		intron	N/A	ENSP00000383163.1
	PCBP3	ENST00000400314.5	TSL:5	c.10+9992A>G		intron	N/A	ENSP00000383168.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118322 AN: 151826 Hom.: 46691 Cov.: 30

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.779 AC: 118428 AN: 151944 Hom.: 46742 Cov.: 30 AF XY: 0.779 AC XY: 57816 AN XY: 74236

African (AFR) AF: 0.864 AC: 35838 AN: 41484

American (AMR) AF: 0.788 AC: 12048 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2750 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5123 AN: 5144

South Asian (SAS) AF: 0.881 AC: 4233 AN: 4806

European-Finnish (FIN) AF: 0.672 AC: 7081 AN: 10536

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.719 AC: 48860 AN: 67922

Other (OTH) AF: 0.797 AC: 1676 AN: 2102

Alfa AF: 0.749 Hom.: 7503

Bravo AF: 0.791

Asia WGS AF: 0.941 AC: 3274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.85
DANN	Benign	0.42
PhyloP100		-1.0
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: rs2839020; hg19: chr21-47280001;