Genetic Variant CITED4:p.Pro80Ala (chr1-40861890-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133467.3(CITED4):c.238C>G(p.Pro80Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CITED4
NM_133467.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

CITED4 (HGNC:18696): (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4) The protein encoded by this intronless gene belongs to the CITED family of transcriptional coactivators that bind to several proteins, including CREB-binding protein (CBP) and p300, via a conserved 32 aa C-terminal motif, and regulate gene transcription. This protein also interacts with transcription factor AP2 (TFAP2), and thus may function as a co-activator for TFAP2. Hypermethylation and transcriptional downregulation of this gene has been observed in oligodendroglial tumors with deletions of chromosomal arms 1p and 19q, and associated with longer recurrence-free and overall survival of patients with oligodendroglial tumors. [provided by RefSeq, Aug 2011]

CITED4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14895451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED4	NM_133467.3 link	c.238C>G	p.Pro80Ala	missense_variant	Exon 1 of 1	ENST00000372638.4	NP_597724.1	Q96RK1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CITED4	ENST00000372638.4 link	c.238C>G	p.Pro80Ala	missense_variant	Exon 1 of 1	6	NM_133467.3	ENSP00000361721.2		Q96RK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1089670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

526034

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238C>G (p.P80A) alteration is located in exon 1 (coding exon 1) of the CITED4 gene. This alteration results from a C to G substitution at nucleotide position 238, causing the proline (P) at amino acid position 80 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

0.058

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.68

REVEL

Benign

0.090

Sift

Benign

0.14

Sift4G

Benign

0.072

Polyphen

0.013

Vest4

0.13

MutPred

0.38

Loss of catalytic residue at P80 (P = 0.0076);

MVP

0.46

MPC

1.0

ClinPred

0.074

GERP RS

4.2

Varity_R

0.035

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over