10-92239999-C-T

Variant summary

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

The NM_014912.5(CPEB3):c.352G>A(p.Ala118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPEB3 NM_014912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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 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=0.07728538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB3	NM_014912.5	c.352G>A	p.Ala118Thr	missense_variant	2/10	ENST00000265997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB3	ENST00000265997.5	c.352G>A	p.Ala118Thr	missense_variant	2/10	1	NM_014912.5
CPEB3	ENST00000412050.8	c.352G>A	p.Ala118Thr	missense_variant	2/10	1		P1
CPEB3	ENST00000614585.4	c.352G>A	p.Ala118Thr	missense_variant	2/10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458958 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725498

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: 9.00e-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

Feb 07, 2023

The c.352G>A (p.A118T) 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 352, causing the alanine (A) at amino acid position 118 to be replaced by a threonine (T). 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	0.061
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	22
Dann	Benign	0.97
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.86	D;D;.
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;N;N
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.39	N;.;N
REVEL	Benign	0.075
Sift	Benign	0.50	T;.;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.014	B;B;B
Vest4		0.10
MutPred		0.16		Gain of disorder (P = 0.0632);Gain of disorder (P = 0.0632);Gain of disorder (P = 0.0632);
MVP		0.21
MPC		0.58
ClinPred		0.22	T
GERP RS		3.9
Varity_R		0.066
gMVP		0.18

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: chr10-93999756;