X-72301950-C-G

Variant names:

Variant summary

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

The NM_001144887.2(CITED1):c.355G>C(p.Gly119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,210,867 control chromosomes in the GnomAD database, including 2 homozygotes. There are 880 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 49 hem., cov: 24)

Exomes 𝑓: 0.0022 ( 2 hom. 831 hem. )

Consequence

CITED1
NM_001144887.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.260

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=0.0067691505).

BS2

High Hemizygotes in GnomAd4 at 49 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED1	NM_001144887.2 link	c.355G>C	p.Gly119Arg	missense_variant	Exon 3 of 3	ENST00000651998.1	NP_001138359.1	Q99966-1
CITED1	NM_001144885.2 link	c.433G>C	p.Gly145Arg	missense_variant	Exon 4 of 4		NP_001138357.1	Q99966-2
CITED1	NM_001144886.2 link	c.355G>C	p.Gly119Arg	missense_variant	Exon 3 of 3		NP_001138358.1	Q99966-1
CITED1	NM_004143.4 link	c.355G>C	p.Gly119Arg	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.355G>C	p.Gly119Arg	missense_variant	Exon 3 of 3		NM_001144887.2	ENSP00000499148.1		Q99966-1
ENSG00000285547	ENST00000648922.1 link	c.1531G>C	p.Gly511Arg	missense_variant	Exon 12 of 12			ENSP00000497072.1		A0A3B3IRV1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

152

AN:

112839

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

AN XY:

34967

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00139

Gnomad ASJ

AF:

0.00790

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000729

Gnomad FIN

AF:

0.000318

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.000659

GnomAD3 exomes

AF:

0.00166

AC:

302

AN:

181951

Hom.:

AF XY:

0.00198

AC XY:

132

AN XY:

66613

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.000439

Gnomad ASJ exome

AF:

0.00859

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00201

Gnomad FIN exome

AF:

0.000943

Gnomad NFE exome

AF:

0.00194

Gnomad OTH exome

AF:

0.00313

GnomAD4 exome

AF:

0.00221

AC:

2422

AN:

1097975

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

831

AN XY:

363349

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.00810

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.000519

Gnomad4 NFE exome

AF:

0.00238

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00135

AC:

152

AN:

112892

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

AN XY:

35030

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00139

Gnomad4 ASJ

AF:

0.00790

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000731

Gnomad4 FIN

AF:

0.000318

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.000651

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00120

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00149

AC:

ExAC

AF:

0.00145

AC:

176

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.433G>C (p.G145R) alteration is located in exon 4 (coding exon 3) of the CITED1 gene. This alteration results from a G to C substitution at nucleotide position 433, causing the glycine (G) at amino acid position 145 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

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

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

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

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.0068

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

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

.;.;M;M;M;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.9

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

REVEL

Benign

0.15

Sift

Benign

0.052

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

Sift4G

Benign

0.067

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

Polyphen

0.72

P;P;B;B;B;.;.

Vest4

0.031

MutPred

0.43

.;.;Loss of catalytic residue at P115 (P = 0.0722);Loss of catalytic residue at P115 (P = 0.0722);Loss of catalytic residue at P115 (P = 0.0722);Loss of catalytic residue at P115 (P = 0.0722);.;

MVP

0.99

MPC

0.71

ClinPred

0.015

GERP RS

4.6

Varity_R

0.14

gMVP

0.52

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