NM_014912.5:c.844G>T

Variant names:

• chr10-92239507-C-A
• NM_014912.5:c.844G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014912.5(CPEB3):​c.844G>T​(p.Val282Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000632 in 1,424,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: CPEB3 NM_014912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2766841).

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.844G>T	p.Val282Leu	missense	Exon 2 of 10	NP_055727.3
	CPEB3	NM_001178137.2		c.844G>T	p.Val282Leu	missense	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.844G>T	p.Val282Leu	missense	Exon 2 of 10	ENSP00000265997.4	Q8NE35-1
	CPEB3	ENST00000412050.8	TSL:1	c.844G>T	p.Val282Leu	missense	Exon 2 of 10	ENSP00000398310.2	Q8NE35-2
	CPEB3	ENST00000903868.1		c.844G>T	p.Val282Leu	missense	Exon 2 of 11	ENSP00000573927.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000632 AC: 9 AN: 1424610 Hom.: 0 Cov.: 31 AF XY: 0.00000709 AC XY: 5 AN XY: 705014

African (AFR) AF: 0.00 AC: 0 AN: 33052

American (AMR) AF: 0.00 AC: 0 AN: 38324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25324

East Asian (EAS) AF: 0.00 AC: 0 AN: 38454

South Asian (SAS) AF: 0.00 AC: 0 AN: 81908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00000824 AC: 9 AN: 1092678

Other (OTH) AF: 0.00 AC: 0 AN: 58940

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.050
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.10
Sift	Benign	0.068	T
Sift4G	Benign	0.37	T
Polyphen		0.10	B
Vest4		0.64
MutPred		0.20		Gain of sheet (P = 0.0477)
MVP		0.32
MPC		0.59
ClinPred		0.88	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.38
Mutation Taster		=82/18	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

hg19: chr10-93999264;