X-72301748-G-A

Position:

chrX-72301748-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001144887.2(CITED1):c.557C>T(p.Thr186Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,210,297 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 186 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.00040 ( 0 hom. 171 hem. )

Consequence

CITED1
NM_001144887.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058149487).

BS2

High Hemizygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CITED1	NM_001144887.2 linkuse as main transcript	c.557C>T	p.Thr186Ile	missense_variant	3/3	ENST00000651998.1	NP_001138359.1	Q99966-1
CITED1	NM_001144885.2 linkuse as main transcript	c.635C>T	p.Thr212Ile	missense_variant	4/4		NP_001138357.1	Q99966-2
CITED1	NM_001144886.2 linkuse as main transcript	c.557C>T	p.Thr186Ile	missense_variant	3/3		NP_001138358.1	Q99966-1
CITED1	NM_004143.4 linkuse as main transcript	c.557C>T	p.Thr186Ile	missense_variant	3/3		NP_004134.2	Q99966-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED1	ENST00000651998.1 linkuse as main transcript	c.557C>T	p.Thr186Ile	missense_variant	3/3		NM_001144887.2	ENSP00000499148.1		Q99966-1

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

112500

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

AN XY:

34640

show subpopulations

Gnomad AFR

AF:

0.0000323

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:

0.000645

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000976

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000410

AC:

AN:

182886

Hom.:

AF XY:

0.000341

AC XY:

AN XY:

67434

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:

0.00113

Gnomad NFE exome

AF:

0.000650

Gnomad OTH exome

AF:

0.000885

GnomAD4 exome

AF:

0.000400

AC:

439

AN:

1097797

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

171

AN XY:

363175

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:

0.0000185

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.000443

Gnomad4 OTH exome

AF:

0.000260

GnomAD4 genome

AF:

0.000507

AC:

AN:

112500

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

AN XY:

34640

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000645

Gnomad4 NFE

AF:

0.000976

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000653

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.635C>T (p.T212I) 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 635, causing the threonine (T) at amino acid position 212 to be replaced by an isoleucine (I). 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

0.28

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.071

.;.;T;T;T

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.84

.;T;T;.;.

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.50

.;.;N;N;N

MutationTaster

Benign

0.59

D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.97

N;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.57

T;T;T;T;T

Sift4G

Benign

0.55

T;T;T;T;T

Polyphen

0.38

B;B;B;B;B

Vest4

0.12

MVP

0.98

MPC

0.27

ClinPred

0.037

GERP RS

5.3

Varity_R

0.15

gMVP

0.22

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