5-173890317-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_030627.4(CPEB4):c.584T>C(p.Val195Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPEB4 NM_030627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25

Genes affected

CPEB4 (HGNC:21747): (cytoplasmic polyadenylation element binding protein 4) Enables RNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; negative regulation of cytoplasmic translation; and response to ischemia. Located in cytoplasm and nucleus. Biomarker of liver cirrhosis; portal hypertension; and primary biliary cholangitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CPEB4
• BP4: Computational evidence support a benign effect (MetaRNN=0.18892887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB4	NM_030627.4	c.584T>C	p.Val195Ala	missense_variant	1/10	ENST00000265085.10
CPEB4	NM_001308189.2	c.584T>C	p.Val195Ala	missense_variant	1/9
CPEB4	NM_001308191.2	c.584T>C	p.Val195Ala	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB4	ENST00000265085.10	c.584T>C	p.Val195Ala	missense_variant	1/10	1	NM_030627.4
CPEB4	ENST00000334035.9	c.584T>C	p.Val195Ala	missense_variant	1/9	1		A1
CPEB4	ENST00000520867.5	c.584T>C	p.Val195Ala	missense_variant	1/8	1		P4
CPEB4	ENST00000519835.5	c.584T>C	p.Val195Ala	missense_variant	1/7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.584T>C (p.V195A) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a T to C substitution at nucleotide position 584, causing the valine (V) at amino acid position 195 to be replaced by an alanine (A). 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
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	23
Dann	Uncertain	0.98
DEOGEN2	Benign	0.026	T;.;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.88	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.065	T;T;T;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.32
MutPred		0.28		Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);
MVP		0.62
MPC		0.50
ClinPred		0.62	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-173317320;