3-51961218-A-G

Variant summary

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

The NM_001174100.2(PCBP4):c.23T>C(p.Leu8Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PCBP4 NM_001174100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

Genes affected

PCBP4 (HGNC:8652): (poly(rC) binding protein 4) 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. This gene is induced by the p53 tumor suppressor, and the encoded protein can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G(2)-M. This gene's protein is found in the cytoplasm, yet it lacks the nuclear localization signals found in other subfamily members. Multiple alternatively spliced transcript variants have been described, but the full-length nature for only some has been determined. [provided by RefSeq, Jul 2008]

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=0.16952538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCBP4	NM_001174100.2	c.23T>C	p.Leu8Pro	missense_variant	3/14	ENST00000461554.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBP4	ENST00000461554.6	c.23T>C	p.Leu8Pro	missense_variant	3/14	1	NM_001174100.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460486 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726608

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2022

The c.23T>C (p.L8P) alteration is located in exon 3 (coding exon 1) of the PCBP4 gene. This alteration results from a T to C substitution at nucleotide position 23, causing the leucine (L) at amino acid position 8 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.;T;T;.;T;T;T;T;T;T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;N;N;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.28	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D;D;D;T;D;D
Sift4G	Benign	0.081	T;T;T;T;T;T;.;.;.;.;.;.;T
Polyphen		0.013	B;B;B;B;B;B;.;.;.;.;.;.;.
Vest4		0.49
MutPred		0.32		Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);Gain of glycosylation at S4 (P = 0.0136);
MVP		0.52
MPC		0.70
ClinPred		0.54	D
GERP RS		5.3
Varity_R		0.21
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-51995234;