rs10509643

Variant names:

• chr10-92155896-G-A
• rs10509643
• NM_014912.5:c.1223-10811C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014912.5(CPEB3):​c.1223-10811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,894 control chromosomes in the GnomAD database, including 1,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1447 hom., cov: 32)
• Consequence: CPEB3 NM_014912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 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.1223-10811C>T		intron	N/A	NP_055727.3
	CPEB3	NM_001178137.2		c.1154-10784C>T		intron	N/A	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.1223-10811C>T		intron	N/A	ENSP00000265997.4	Q8NE35-1
	CPEB3	ENST00000412050.8	TSL:1	c.1154-10784C>T		intron	N/A	ENSP00000398310.2	Q8NE35-2
	CPEB3	ENST00000903868.1		c.1246+2153C>T		intron	N/A	ENSP00000573927.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15537 AN: 151776 Hom.: 1442 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15567 AN: 151894 Hom.: 1447 Cov.: 32 AF XY: 0.102 AC XY: 7577 AN XY: 74252

African (AFR) AF: 0.227 AC: 9383 AN: 41396

American (AMR) AF: 0.160 AC: 2434 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3464

East Asian (EAS) AF: 0.208 AC: 1075 AN: 5156

South Asian (SAS) AF: 0.0237 AC: 114 AN: 4816

European-Finnish (FIN) AF: 0.0400 AC: 420 AN: 10508

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1611 AN: 67988

Other (OTH) AF: 0.102 AC: 214 AN: 2106

Alfa AF: 0.0515 Hom.: 2118

Bravo AF: 0.122

Asia WGS AF: 0.103 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.39
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10509643;

hg19: chr10-93915653;

COSMIC: COSV56464149;