21-45899581-A-AT

Position:

• chr21-45899581-A-AT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001384156.1(PCBP3):​c.166-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,455,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (0 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 21-45899581-A-AT is Benign according to our data. Variant chr21-45899581-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 3055844.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.166-8dupT		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.166-18_166-17insT		intron_variant			NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.000174 AC: 26 AN: 149638 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000178

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00371 AC: 4850 AN: 1305882 Hom.: 0 Cov.: 28 AF XY: 0.00345 AC XY: 2241 AN XY: 650348

Gnomad4 AFR exome AF: 0.00312

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00225

Gnomad4 EAS exome AF: 0.00162

Gnomad4 SAS exome AF: 0.00342

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.00410

Gnomad4 OTH exome AF: 0.00331

GnomAD4 genome AF: 0.000174 AC: 26 AN: 149732 Hom.: 0 Cov.: 33 AF XY: 0.000219 AC XY: 16 AN XY: 72978

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.000265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.00150

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000178

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000174

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 04, 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)		0.010		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;