21-45899581-AT-A

Position:

• chr21-45899581-AT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001384156.1(PCBP3):​c.166-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,484,948 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00091 (2 hom.)
• Consequence: PCBP3 NM_001384156.1 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.14

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 21-45899581-AT-A is Benign according to our data. Variant chr21-45899581-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039600.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.166-8delT		splice_region_variant, intron_variant		ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.166-17delT		intron_variant			NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.000154 AC: 23 AN: 149644 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00353

Gnomad SAS AF: 0.000427

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000911 AC: 1216 AN: 1335210 Hom.: 2 Cov.: 28 AF XY: 0.000841 AC XY: 559 AN XY: 664934

Gnomad4 AFR exome AF: 0.000887

Gnomad4 AMR exome AF: 0.000564

Gnomad4 ASJ exome AF: 0.000336

Gnomad4 EAS exome AF: 0.00484

Gnomad4 SAS exome AF: 0.00104

Gnomad4 FIN exome AF: 0.000306

Gnomad4 NFE exome AF: 0.000818

Gnomad4 OTH exome AF: 0.000961

GnomAD4 genome AF: 0.000154 AC: 23 AN: 149738 Hom.: 0 Cov.: 33 AF XY: 0.000123 AC XY: 9 AN XY: 72984

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00354

Gnomad4 SAS AF: 0.000428

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00589 Hom.: 0

Bravo AF: 0.000242

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PCBP3-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs145892465; hg19: chr21-47319495;