5-173890363-C-A

Variant names:

• chr5-173890363-C-A
• NM_030627.4:c.630C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030627.4(CPEB4):​c.630C>A​(p.Phe210Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: -0.214

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB4	NM_030627.4	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 10	ENST00000265085.10	NP_085130.2
CPEB4	NM_001308189.2	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 9		NP_001295118.1
CPEB4	NM_001308191.2	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 8		NP_001295120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 10	1	NM_030627.4	ENSP00000265085.5
CPEB4	ENST00000334035.9	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 9	1		ENSP00000334533.5
CPEB4	ENST00000520867.5	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 8	1		ENSP00000429092.1
CPEB4	ENST00000519835.5	c.630C>A	p.Phe210Leu	missense_variant	Exon 1 of 7	1		ENSP00000429048.1

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

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.630C>A (p.F210L) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a C to A substitution at nucleotide position 630, causing the phenylalanine (F) at amino acid position 210 to be replaced by a leucine (L). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.9	L;.;L;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		1.0	D;D;D;P
Vest4		0.74
MutPred		0.33		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.53
MPC		1.4
ClinPred		1.0	D
GERP RS		-7.6
Varity_R		0.47
gMVP		0.53

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: chr5-173317366; COSMIC: COSV54170880; COSMIC: COSV54170880;