chr21-45930812-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384156.1(PCBP3):​c.823G>C​(p.Glu275Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
• Consequence: PCBP3 NM_001384156.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.823G>C	p.Glu275Gln	missense_variant	Exon 15 of 18	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.823G>C	p.Glu275Gln	missense_variant	Exon 15 of 18		NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 24

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74384

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;.;.;T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D;D;T;D;T;.
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;.;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.31	N;N;N;.;N;N
REVEL	Benign	0.065
Sift	Benign	0.56	T;T;T;.;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.054	B;B;D;B;.;B
Vest4		0.53
MutPred		0.24		Loss of phosphorylation at S273 (P = 0.0987);.;.;.;.;.;
MVP		0.63
MPC		0.44
ClinPred		0.39	T
GERP RS		4.4
Varity_R		0.16
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: -26

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

Publications

LitVar

Other links and lift over

dbSNP: rs747312227; hg19: chr21-47350726;