21-45899581-ATTTT-AT

Variant names:

• chr21-45899581-ATTT-A
• rs145892465
• NM_001384156.1:c.166-10_166-8delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001384156.1(PCBP3):​c.166-10_166-8delTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000743 in 1,346,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PCBP3 NM_001384156.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.166-10_166-8delTTT		splice_region intron	N/A	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.166-10_166-8delTTT		splice_region intron	N/A	NP_001335169.1
	PCBP3	NM_001382279.1		c.166-10_166-8delTTT		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.166-17_166-15delTTT		intron	N/A	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.70-17_70-15delTTT		intron	N/A	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.166-17_166-15delTTT		intron	N/A	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1346432 Hom.: 0 AF XY: 0.00000149 AC XY: 1 AN XY: 670512

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

African (AFR) AF: 0.00 AC: 0 AN: 30704

American (AMR) AF: 0.00 AC: 0 AN: 41160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23954

East Asian (EAS) AF: 0.00 AC: 0 AN: 36596

South Asian (SAS) AF: 0.00 AC: 0 AN: 78512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5448

European-Non Finnish (NFE) AF: 9.76e-7 AC: 1 AN: 1025060

Other (OTH) AF: 0.00 AC: 0 AN: 55620

⚠️ 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

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;