X-72301959-C-T

Position:

chrX-72301959-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001144887.2(CITED1):c.346G>A(p.Gly116Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,210,630 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000021 ( 0 hom. 10 hem. )

Consequence

CITED1
NM_001144887.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.161

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12839898).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CITED1	NM_001144887.2 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant	3/3	ENST00000651998.1	NP_001138359.1	Q99966-1
CITED1	NM_001144885.2 linkuse as main transcript	c.424G>A	p.Gly142Arg	missense_variant	4/4		NP_001138357.1	Q99966-2
CITED1	NM_001144886.2 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant	3/3		NP_001138358.1	Q99966-1
CITED1	NM_004143.4 linkuse as main transcript	c.346G>A	p.Gly116Arg	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.346G>A	p.Gly116Arg	missense_variant	3/3		NM_001144887.2	ENSP00000499148.1		Q99966-1
ENSG00000285547	ENST00000648922.1 linkuse as main transcript	c.1522G>A	p.Gly508Arg	missense_variant	12/12			ENSP00000497072.1		A0A3B3IRV1

Frequencies

GnomAD3 genomes

AF:

0.00000886

AC:

AN:

112819

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34959

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000607

AC:

AN:

181328

Hom.:

AF XY:

0.0000605

AC XY:

AN XY:

66098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000220

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1097811

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

363207

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000886

AC:

AN:

112819

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34959

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:

0.0000187

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000741

AC:

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

Apr 19, 2023

The c.424G>A (p.G142R) alteration is located in exon 4 (coding exon 3) of the CITED1 gene. This alteration results from a G to A substitution at nucleotide position 424, causing the glycine (G) at amino acid position 142 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;.;T;T;T;T;.

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.79

.;T;T;.;.;T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.13

T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

.;.;L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

N;N;N;N;N;D;.

REVEL

Benign

0.13

Sift

Benign

0.030

D;D;T;T;T;D;.

Sift4G

Benign

0.22

T;T;T;T;T;.;.

Polyphen

0.18

B;B;B;B;B;.;.

Vest4

0.039

MutPred

0.60

.;.;Loss of catalytic residue at P112 (P = 0.0722);Loss of catalytic residue at P112 (P = 0.0722);Loss of catalytic residue at P112 (P = 0.0722);Loss of catalytic residue at P112 (P = 0.0722);.;

MVP

0.97

MPC

0.68

ClinPred

0.066

GERP RS

3.9

Varity_R

0.096

gMVP

0.44

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