Variant X-72302147-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144887.2(CITED1):c.158A>G(p.Asn53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,082,476 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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: not found (cov: 23)

Exomes 𝑓: 0.0000065 ( 0 hom. 5 hem. )

Consequence

CITED1
NM_001144887.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.985

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:

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14504158).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CITED1	NM_001144887.2 linkuse as main transcript	c.158A>G	p.Asn53Ser	missense_variant	3/3	ENST00000651998.1	NP_001138359.1
CITED1	NM_001144885.2 linkuse as main transcript	c.236A>G	p.Asn79Ser	missense_variant	4/4		NP_001138357.1
CITED1	NM_001144886.2 linkuse as main transcript	c.158A>G	p.Asn53Ser	missense_variant	3/3		NP_001138358.1
CITED1	NM_004143.4 linkuse as main transcript	c.158A>G	p.Asn53Ser	missense_variant	3/3		NP_004134.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED1	ENST00000651998.1 linkuse as main transcript	c.158A>G	p.Asn53Ser	missense_variant	3/3		NM_001144887.2	ENSP00000499148	P2	Q99966-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149161

Hom.:

AF XY:

0.0000220

AC XY:

AN XY:

45441

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:

0.0000161

Gnomad OTH exome

AF:

0.000252

GnomAD4 exome

AF:

0.00000647

AC:

AN:

1082476

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

353072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000757

Gnomad4 NFE exome

AF:

0.00000480

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000223

Hom.:

ExAC

AF:

0.00000830

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

Dec 16, 2023

The c.236A>G (p.N79S) alteration is located in exon 4 (coding exon 3) of the CITED1 gene. This alteration results from a A to G substitution at nucleotide position 236, causing the asparagine (N) at amino acid position 79 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

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

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.015

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

.;.;N;N;N;.;.;.;.

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.036

Sift

Benign

0.083

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

Sift4G

Benign

0.23

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

Polyphen

0.087

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

Vest4

0.15

MutPred

0.37

.;.;Gain of glycosylation at N53 (P = 5e-04);Gain of glycosylation at N53 (P = 5e-04);Gain of glycosylation at N53 (P = 5e-04);Gain of glycosylation at N53 (P = 5e-04);.;.;.;

MVP

0.81

MPC

0.15

ClinPred

0.056

GERP RS

1.8

Varity_R

0.059

gMVP

0.15

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