X-72301745-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001144887.2(CITED1):c.560C>T(p.Ala187Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000909 in 1,209,994 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000098 ( 0 hom. 30 hem. )

Consequence

CITED1
NM_001144887.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

Variant links:

Genes affected

CITED1 (HGNC:1986): (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1) This gene encodes a member of the CREB-binding protein/p300-interacting transactivator with Asp/Glu-rich C-terminal domain (CITED) family of proteins. The encoded protein, also known as melanocyte-specific gene 1, may function as a transcriptional coactivator and may play a role in pigmentation of melanocytes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]

CITED1 links:

ENSG00000285547 (HGNC:):

ENSG00000285547 links:

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

PIN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2652412).

BS2

High Hemizygotes in GnomAdExome4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED1	NM_001144887.2 link	c.560C>T	p.Ala187Val	missense_variant	Exon 3 of 3	ENST00000651998.1	NP_001138359.1	Q99966-1
CITED1	NM_001144885.2 link	c.638C>T	p.Ala213Val	missense_variant	Exon 4 of 4		NP_001138357.1	Q99966-2
CITED1	NM_001144886.2 link	c.560C>T	p.Ala187Val	missense_variant	Exon 3 of 3		NP_001138358.1	Q99966-1
CITED1	NM_004143.4 link	c.560C>T	p.Ala187Val	missense_variant	Exon 3 of 3		NP_004134.2	Q99966-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CITED1	ENST00000651998.1 link	c.560C>T	p.Ala187Val	missense_variant	Exon 3 of 3		NM_001144887.2	ENSP00000499148.1		Q99966-1
ENSG00000285547	ENST00000648922.1 link	c.*66C>T		downstream_gene_variant				ENSP00000497072.1		A0A3B3IRV1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112366

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34530

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182756

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000491

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000984

AC:

108

AN:

1097628

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

363018

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.000126

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112366

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34530

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.638C>T (p.A213V) alteration is located in exon 4 (coding exon 3) of the CITED1 gene. This alteration results from a C to T substitution at nucleotide position 638, causing the alanine (A) at amino acid position 213 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;.;T;T;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

.;T;T;.;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L;L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

N;N;N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0080

D;D;D;D;D

Sift4G

Uncertain

0.056

T;T;D;D;D

Polyphen

0.015

B;B;B;B;B

Vest4

0.39

MutPred

0.53

.;.;Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);

MVP

0.96

MPC

0.66

ClinPred

0.48

GERP RS

3.5

Varity_R

0.14

gMVP

0.40

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