10-92239511-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_014912.5(CPEB3):c.840C>T(p.Val280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,574,952 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (62 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: CPEB3 NM_014912.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 10-92239511-G-A is Benign according to our data. Variant chr10-92239511-G-A is described in ClinVar as [Benign]. Clinvar id is 785323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.319 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB3	NM_014912.5	c.840C>T	p.Val280=	synonymous_variant	2/10	ENST00000265997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB3	ENST00000265997.5	c.840C>T	p.Val280=	synonymous_variant	2/10	1	NM_014912.5
CPEB3	ENST00000412050.8	c.840C>T	p.Val280=	synonymous_variant	2/10	1		P1
CPEB3	ENST00000614585.4	c.840C>T	p.Val280=	synonymous_variant	2/10	5

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2406 AN: 152156 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00410 AC: 751 AN: 183054 Hom.: 16 AF XY: 0.00310 AC XY: 303 AN XY: 97634

Gnomad AFR exome AF: 0.0593

Gnomad AMR exome AF: 0.00228

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000199

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.00165 AC: 2346 AN: 1422678 Hom.: 64 Cov.: 31 AF XY: 0.00141 AC XY: 989 AN XY: 703878

Gnomad4 AFR exome AF: 0.0587

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000183

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000815

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.0158 AC: 2410 AN: 152274 Hom.: 62 Cov.: 32 AF XY: 0.0156 AC XY: 1162 AN XY: 74468

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00761 Hom.: 11

Bravo AF: 0.0181

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	5.9
Dann	Benign	0.97

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: rs115735799; hg19: chr10-93999268;