21-45899581-ATTTT-ATTT

Variant names:

• chr21-45899581-AT-A
• rs145892465
• NM_001384156.1:c.166-8delT

Variant summary

Our verdict is Likely benign. The variant received -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
• 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: Likely_benign. The variant received -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 VariationId is 3039600.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	NM_001384156.1	MANE Select	c.166-8delT		splice_region intron	N/A	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.166-8delT		splice_region intron	N/A	NP_001335169.1
	PCBP3	NM_001382279.1		c.166-8delT		splice_region intron	N/A	NP_001369208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.166-17delT		intron	N/A	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.70-17delT		intron	N/A	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.166-17delT		intron	N/A	ENSP00000383163.1	P57721-2

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

GnomAD2 exomes AF: 0.00212 AC: 353 AN: 166326 AF XY: 0.00194

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.0102

Gnomad FIN exome AF: 0.000894

Gnomad NFE exome AF: 0.00154

Gnomad OTH exome AF: 0.00274

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000887 AC: 27 AN: 30432

American (AMR) AF: 0.000564 AC: 23 AN: 40746

Ashkenazi Jewish (ASJ) AF: 0.000336 AC: 8 AN: 23788

East Asian (EAS) AF: 0.00484 AC: 176 AN: 36350

South Asian (SAS) AF: 0.00104 AC: 81 AN: 77760

European-Finnish (FIN) AF: 0.000306 AC: 15 AN: 49066

Middle Eastern (MID) AF: 0.000370 AC: 2 AN: 5410

European-Non Finnish (NFE) AF: 0.000818 AC: 831 AN: 1016482

Other (OTH) AF: 0.000961 AC: 53 AN: 55176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0000246 AC: 1 AN: 40698

American (AMR) AF: 0.00 AC: 0 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00354 AC: 18 AN: 5084

South Asian (SAS) AF: 0.000428 AC: 2 AN: 4672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67390

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00589 Hom.: 0

Bravo AF: 0.000242

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PCBP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

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: rs145892465; hg19: chr21-47319495;