5-173932479-G-T

Variant names:

• chr5-173932479-G-T
• rs749355575
• NM_030627.4:c.1237G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030627.4(CPEB4):​c.1237G>T​(p.Asp413Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D413N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPEB4 NM_030627.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030627.4. 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
	CPEB4	NM_030627.4	MANE Select	c.1237G>T	p.Asp413Tyr	missense	Exon 3 of 10	NP_085130.2	Q17RY0-1
	CPEB4	NM_001308192.2		c.91G>T	p.Asp31Tyr	missense	Exon 3 of 9	NP_001295121.1	E5RFP2
	CPEB4	NM_001308189.2		c.1208-10547G>T		intron	N/A	NP_001295118.1	Q17RY0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB4	ENST00000265085.10	TSL:1 MANE Select	c.1237G>T	p.Asp413Tyr	missense	Exon 3 of 10	ENSP00000265085.5	Q17RY0-1
	CPEB4	ENST00000334035.9	TSL:1	c.1208-10547G>T		intron	N/A	ENSP00000334533.5	Q17RY0-2
	CPEB4	ENST00000520867.5	TSL:1	c.1208-12488G>T		intron	N/A	ENSP00000429092.1	B7ZLQ8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.86	P
Vest4		0.72
MutPred		0.38		Loss of disorder (P = 0.0354)
MVP		0.88
MPC		0.74
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.91
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs749355575; hg19: chr5-173359482;