10-92111170-T-C

Variant names:

• chr10-92111170-T-C
• NM_014912.5:c.1478A>G

Variant summary

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

The NM_014912.5(CPEB3):​c.1478A>G​(p.Glu493Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPEB3 NM_014912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB3	NM_014912.5	c.1478A>G	p.Glu493Gly	missense_variant	Exon 7 of 10	ENST00000265997.5	NP_055727.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB3	ENST00000265997.5	c.1478A>G	p.Glu493Gly	missense_variant	Exon 7 of 10	1	NM_014912.5	ENSP00000265997.4
CPEB3	ENST00000412050.8	c.1436A>G	p.Glu479Gly	missense_variant	Exon 7 of 10	1		ENSP00000398310.2
CPEB3	ENST00000614585.4	c.1478A>G	p.Glu493Gly	missense_variant	Exon 7 of 10	5		ENSP00000482128.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1478A>G (p.E493G) alteration is located in exon 7 (coding exon 6) of the CPEB3 gene. This alteration results from a A to G substitution at nucleotide position 1478, causing the glutamic acid (E) at amino acid position 493 to be replaced by a glycine (G). 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	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;.
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.8	D;.;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D;.;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.93	P;B;B
Vest4		0.67
MutPred		0.37		.;Loss of stability (P = 0.06);Loss of stability (P = 0.06);
MVP		0.44
MPC		0.77
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.53
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-93870927;