chr21-45714069-A-T

Position:

• chr21-45714069-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
PCBP3	NM_001384156.1	c.-199-21323A>T		intron_variant		ENST00000681687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBP3	ENST00000681687.1	c.-199-21323A>T		intron_variant			NM_001384156.1	P4
PCBP3	ENST00000400314.5	c.-163-21323A>T		intron_variant		5		P4
PCBP3	ENST00000465077.5	n.176-14607A>T		intron_variant, non_coding_transcript_variant		3
PCBP3	ENST00000594149.5	n.182-21323A>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.00527

Gnomad4 OTH AF: 0.0492

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

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: rs10483081; hg19: chr21-47133983;