Variant 10-92239705-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014912.5(CPEB3):c.646A>G(p.Met216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,567,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

CPEB3
NM_014912.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08197972).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB3	NM_014912.5 linkuse as main transcript	c.646A>G	p.Met216Val	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.646A>G	p.Met216Val	missense_variant	2/10	1	NM_014912.5		Q8NE35-1
CPEB3	ENST00000412050.8 linkuse as main transcript	c.646A>G	p.Met216Val	missense_variant	2/10	1		P1	Q8NE35-2
CPEB3	ENST00000614585.4 linkuse as main transcript	c.646A>G	p.Met216Val	missense_variant	2/10	5			Q8NE35-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

178408

Hom.:

AF XY:

0.0000304

AC XY:

AN XY:

98554

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000494

AC:

AN:

1415736

Hom.:

Cov.:

AF XY:

0.00000428

AC XY:

AN XY:

700734

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:

0.0000871

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000344

AC:

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

Aug 17, 2022

The c.646A>G (p.M216V) alteration is located in exon 2 (coding exon 1) of the CPEB3 gene. This alteration results from a A to G substitution at nucleotide position 646, causing the methionine (M) at amino acid position 216 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.012

.;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.84

T;T;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

0.71

N;N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.91

N;.;N

REVEL

Benign

0.11

Sift

Benign

0.22

T;.;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.59

MutPred

0.29

Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);

MVP

0.40

MPC

0.62

ClinPred

0.035

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.35

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