Variant 10-92239525-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014912.5(CPEB3):c.826G>A(p.Val276Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,412,208 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: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CPEB3
NM_014912.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

CPEB3 (HGNC:21746): (cytoplasmic polyadenylation element binding protein 3) Enables mRNA 3'-UTR binding activity and translation factor activity, RNA binding. Involved in cellular response to amino acid stimulus; negative regulation of transcription by RNA polymerase II; and positive regulation of mRNA catabolic process. Located in several cellular components, including cytosol; midbody; and nucleoplasm. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

CPEB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4108401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB3	NM_014912.5 linkuse as main transcript	c.826G>A	p.Val276Met	missense_variant	2/10	ENST00000265997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB3	ENST00000265997.5 linkuse as main transcript	c.826G>A	p.Val276Met	missense_variant	2/10	1	NM_014912.5		Q8NE35-1
CPEB3	ENST00000412050.8 linkuse as main transcript	c.826G>A	p.Val276Met	missense_variant	2/10	1		P1	Q8NE35-2
CPEB3	ENST00000614585.4 linkuse as main transcript	c.826G>A	p.Val276Met	missense_variant	2/10	5			Q8NE35-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000591

AC:

AN:

169134

Hom.:

AF XY:

0.0000111

AC XY:

AN XY:

89808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000764

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412208

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697644

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2022

The c.826G>A (p.V276M) alteration is located in exon 2 (coding exon 1) of the CPEB3 gene. This alteration results from a G to A substitution at nucleotide position 826, causing the valine (V) at amino acid position 276 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;D;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.26

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.44

T;.;T

Sift4G

Benign

0.30

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.58

MutPred

0.24

Gain of catalytic residue at V272 (P = 0.0302);Gain of catalytic residue at V272 (P = 0.0302);Gain of catalytic residue at V272 (P = 0.0302);

MVP

0.49

MPC

1.4

ClinPred

0.68

GERP RS

3.5

Varity_R

0.084

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over