10-92239507-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_014912.5(CPEB3):c.844G>T(p.Val282Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000632 in 1,424,610 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: 0.0000063 (0 hom.)
• Consequence: CPEB3 NM_014912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2766841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB3	NM_014912.5	c.844G>T	p.Val282Leu	missense_variant	2/10	ENST00000265997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB3	ENST00000265997.5	c.844G>T	p.Val282Leu	missense_variant	2/10	1	NM_014912.5
CPEB3	ENST00000412050.8	c.844G>T	p.Val282Leu	missense_variant	2/10	1		P1
CPEB3	ENST00000614585.4	c.844G>T	p.Val282Leu	missense_variant	2/10	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000632 AC: 9 AN: 1424610 Hom.: 0 Cov.: 31 AF XY: 0.00000709 AC XY: 5 AN XY: 705014

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: 0.00000824

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jan 26, 2023

The c.844G>T (p.V282L) alteration is located in exon 2 (coding exon 1) of the CPEB3 gene. This alteration results from a G to T substitution at nucleotide position 844, causing the valine (V) at amino acid position 282 to be replaced by a leucine (L). 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	0.20
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
Cadd	Pathogenic	28
Dann	Uncertain	0.99
Eigen	Benign	-0.050
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	D;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	0.67	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.55	N;.;N
REVEL	Benign	0.10
Sift	Benign	0.068	T;.;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.10	B;P;P
Vest4		0.64
MutPred		0.20		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.32
MPC		0.59
ClinPred		0.88	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.38

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: chr10-93999264;