15-82553914-C-T

Variant names:

• chr15-82553914-C-T
• rs752604379
• NM_001365242.1:c.1018G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365242.1(CPEB1):​c.1018G>A​(p.Val340Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CPEB1 NM_001365242.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75

Genes affected

CPEB1 (HGNC:21744): (cytoplasmic polyadenylation element binding protein 1) This gene encodes a member of the cytoplasmic polyadenylation element binding protein family. This highly conserved protein binds to a specific RNA sequence, called the cytoplasmic polyadenylation element, found in the 3' untranslated region of some mRNAs. The encoded protein functions in both the cytoplasm and the nucleus. It is involved in the regulation of mRNA translation, as well as processing of the 3' untranslated region, and may play a role in cell proliferation and tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ENSG00000260836 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB1	NM_001365242.1	c.1018G>A	p.Val340Met	missense_variant	Exon 7 of 13	ENST00000684509.1	NP_001352171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB1	ENST00000684509.1	c.1018G>A	p.Val340Met	missense_variant	Exon 7 of 13		NM_001365242.1	ENSP00000507835.1
ENSG00000260836	ENST00000562833.2	c.712G>A	p.Val238Met	missense_variant	Exon 4 of 13	3		ENSP00000454786.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000805 AC: 2 AN: 248372 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134798

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460676 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 05, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.937G>A (p.V313M) alteration is located in exon 6 (coding exon 6) of the CPEB1 gene. This alteration results from a G to A substitution at nucleotide position 937, causing the valine (V) at amino acid position 313 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
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;.;.;.;.;.;.;.;.;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;D;.;.;.;D;.;.;.;.;.
M_CAP	Benign	0.0076	T
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	.;.;.;.;.;L;.;.;.;.;.
PrimateAI	Pathogenic	0.85	D
Sift4G	Pathogenic	0.0010	.;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;.;D;.;.;.;.;.
Vest4		0.81, 0.81, 0.85, 0.80, 0.85, 0.79, 0.85, 0.85
MutPred		0.49		.;.;Loss of catalytic residue at V313 (P = 0.0866);.;.;Loss of catalytic residue at V313 (P = 0.0866);.;.;.;.;.;
MVP		0.94
ClinPred		0.91	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.83

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

Other links and lift over

dbSNP: rs752604379; hg19: chr15-83222664;