21-45930793-G-T

Variant names:

• chr21-45930793-G-T
• NM_001384156.1:c.804G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384156.1(PCBP3):​c.804G>T​(p.Lys268Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000819 in 1,220,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1989584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.804G>T	p.Lys268Asn	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.804G>T	p.Lys268Asn	missense_variant	Exon 15 of 18		NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.19e-7 AC: 1 AN: 1220508 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 620272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.077	T;.;.;T;.;T
Eigen	Benign	-0.0013
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D;D;T;D;T;.
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	N;N;N;.;N;N
REVEL	Benign	0.056
Sift	Benign	0.54	T;T;T;.;T;T
Sift4G	Benign	0.46	T;T;T;T;T;T
Polyphen		0.95	P;B;D;B;.;B
Vest4		0.59
MutPred		0.38		Loss of ubiquitination at K268 (P = 0.0037);.;.;.;.;.;
MVP		0.46
MPC		0.52
ClinPred		0.56	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47350707;