X-72301950-C-G

Variant names:

• chrX-72301950-C-G
• rs147699506
• NM_001144887.2:c.355G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 12/21 in silico tools predict 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.260
• Publications: 3 publications found

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]

ENSG00000285547 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067691505).
• BS2: High Hemizygotes in GnomAd4 at 49 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144887.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED1	NM_001144887.2	MANE Select	c.355G>C	p.Gly119Arg	missense	Exon 3 of 3	NP_001138359.1	Q99966-1
	CITED1	NM_001144885.2		c.433G>C	p.Gly145Arg	missense	Exon 4 of 4	NP_001138357.1	Q99966-2
	CITED1	NM_001144886.2		c.355G>C	p.Gly119Arg	missense	Exon 3 of 3	NP_001138358.1	Q99966-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED1	ENST00000651998.1	MANE Select	c.355G>C	p.Gly119Arg	missense	Exon 3 of 3	ENSP00000499148.1	Q99966-1
	ENSG00000285547	ENST00000648922.1		c.1531G>C	p.Gly511Arg	missense	Exon 12 of 12	ENSP00000497072.1	A0A3B3IRV1
	CITED1	ENST00000246139.9	TSL:1	c.355G>C	p.Gly119Arg	missense	Exon 3 of 3	ENSP00000246139.5	Q99966-1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 152 AN: 112839 Hom.: 0 Cov.: 24

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

GnomAD2 exomes AF: 0.00166 AC: 302 AN: 181951 AF XY: 0.00198

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 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.: 2 Cov.: 30 AF XY: 0.00229 AC XY: 831 AN XY: 363349

African (AFR) AF: 0.0000758 AC: 2 AN: 26396

American (AMR) AF: 0.000426 AC: 15 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00810 AC: 157 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00213 AC: 115 AN: 54099

European-Finnish (FIN) AF: 0.000519 AC: 21 AN: 40488

Middle Eastern (MID) AF: 0.000967 AC: 4 AN: 4136

European-Non Finnish (NFE) AF: 0.00238 AC: 2003 AN: 842025

Other (OTH) AF: 0.00228 AC: 105 AN: 46072

GnomAD4 genome AF: 0.00135 AC: 152 AN: 112892 Hom.: 0 Cov.: 24 AF XY: 0.00140 AC XY: 49 AN XY: 35030

African (AFR) AF: 0.000290 AC: 9 AN: 31067

American (AMR) AF: 0.00139 AC: 15 AN: 10782

Ashkenazi Jewish (ASJ) AF: 0.00790 AC: 21 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3581

South Asian (SAS) AF: 0.000731 AC: 2 AN: 2735

European-Finnish (FIN) AF: 0.000318 AC: 2 AN: 6290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00191 AC: 102 AN: 53340

Other (OTH) AF: 0.000651 AC: 1 AN: 1536

Alfa AF: 0.00284 Hom.: 23

Bravo AF: 0.00120

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00173 AC: 5

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00149 AC: 10

ExAC AF: 0.00145 AC: 176

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.26
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.052	T
Sift4G	Benign	0.067	T
Polyphen		0.72	P
Vest4		0.031
MutPred		0.43		Loss of catalytic residue at P115 (P = 0.0722)
MVP		0.99
MPC		0.71
ClinPred		0.015	T
GERP RS		4.6
Varity_R		0.14
gMVP		0.52
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs147699506; hg19: chrX-71521800;