NM_014912.5:c.840C>T

Variant names:

• chr10-92239511-G-A
• rs115735799
• NM_014912.5:c.840C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014912.5(CPEB3):​c.840C>T​(p.Val280Val) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.319
• Publications: 1 publications found

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]

CPEB3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 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 VariationId is 785323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	NM_014912.5	MANE Select	c.840C>T	p.Val280Val	synonymous	Exon 2 of 10	NP_055727.3
	CPEB3	NM_001178137.2		c.840C>T	p.Val280Val	synonymous	Exon 2 of 10	NP_001171608.1	Q5QP71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	ENST00000265997.5	TSL:1 MANE Select	c.840C>T	p.Val280Val	synonymous	Exon 2 of 10	ENSP00000265997.4	Q8NE35-1
	CPEB3	ENST00000412050.8	TSL:1	c.840C>T	p.Val280Val	synonymous	Exon 2 of 10	ENSP00000398310.2	Q8NE35-2
	CPEB3	ENST00000903868.1		c.840C>T	p.Val280Val	synonymous	Exon 2 of 11	ENSP00000573927.1

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

GnomAD2 exomes AF: 0.00410 AC: 751 AN: 183054 AF XY: 0.00310

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 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

African (AFR) AF: 0.0587 AC: 1935 AN: 32980

American (AMR) AF: 0.00250 AC: 95 AN: 38034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25312

East Asian (EAS) AF: 0.00 AC: 0 AN: 38342

South Asian (SAS) AF: 0.000183 AC: 15 AN: 81766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50266

Middle Eastern (MID) AF: 0.00234 AC: 13 AN: 5548

European-Non Finnish (NFE) AF: 0.0000815 AC: 89 AN: 1091544

Other (OTH) AF: 0.00338 AC: 199 AN: 58886

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

African (AFR) AF: 0.0557 AC: 2313 AN: 41544

American (AMR) AF: 0.00412 AC: 63 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68012

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00778 Hom.: 12

Bravo AF: 0.0181

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.9
DANN	Benign	0.97
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs115735799; hg19: chr10-93999268;