chr21-45930812-G-T

Variant names:

• chr21-45930812-G-T
• rs747312227
• NM_001384156.1:c.823G>T

Variant summary

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

The NM_001384156.1(PCBP3):​c.823G>T​(p.Glu275*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PCBP3 NM_001384156.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93
• Publications: 3 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.823G>T	p.Glu275*	stop_gained	Exon 15 of 18	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.892G>T	p.Glu298*	stop_gained	Exon 14 of 17	NP_001335169.1
	PCBP3	NM_001382279.1		c.892G>T	p.Glu298*	stop_gained	Exon 12 of 15	NP_001369208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.823G>T	p.Glu275*	stop_gained	Exon 15 of 18	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.793G>T	p.Glu265*	stop_gained	Exon 10 of 13	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.745G>T	p.Glu249*	stop_gained	Exon 10 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	51
DANN	Uncertain	1.0
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		4.9
Vest4		0.28
GERP RS		4.4
Mutation Taster		=27/173	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.37		Position offset: -26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747312227; hg19: chr21-47350726;