Genetic Variant CITED4:p.Val182Gly (chr1-40861583-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_133467.3(CITED4):c.545T>G(p.Val182Gly) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 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: 7.98

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED4	NM_133467.3 link	c.545T>G	p.Val182Gly	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.545T>G	p.Val182Gly	missense_variant	Exon 1 of 1	6	NM_133467.3	ENSP00000361721.2		Q96RK1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150854

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000966

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000109

AC:

141

AN:

1293076

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

638616

show subpopulations

Gnomad4 AFR exome

AF:

0.0000787

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.000183

Gnomad4 EAS exome

AF:

0.000149

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000316

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000398

AC:

AN:

150854

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73650

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000966

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.545T>G (p.V182G) alteration is located in exon 1 (coding exon 1) of the CITED4 gene. This alteration results from a T to G substitution at nucleotide position 545, causing the valine (V) at amino acid position 182 to be replaced by a glycine (G). 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

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.80

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

-0.076

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.33

MutPred

0.58

Gain of relative solvent accessibility (P = 0.005);

MVP

0.62

MPC

2.0

ClinPred

1.0

GERP RS

4.0

Varity_R

0.82

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over