chrX-72301953-C-T

Variant names:

• chrX-72301953-C-T
• rs1174164523
• NM_001144887.2:c.352G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144887.2(CITED1):​c.352G>A​(p.Ala118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,940 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: CITED1 NM_001144887.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.931
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09160927).

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.352G>A	p.Ala118Thr	missense	Exon 3 of 3	NP_001138359.1	Q99966-1
	CITED1	NM_001144885.2		c.430G>A	p.Ala144Thr	missense	Exon 4 of 4	NP_001138357.1	Q99966-2
	CITED1	NM_001144886.2		c.352G>A	p.Ala118Thr	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.352G>A	p.Ala118Thr	missense	Exon 3 of 3	ENSP00000499148.1	Q99966-1
	ENSG00000285547	ENST00000648922.1		c.1528G>A	p.Ala510Thr	missense	Exon 12 of 12	ENSP00000497072.1	A0A3B3IRV1
	CITED1	ENST00000246139.9	TSL:1	c.352G>A	p.Ala118Thr	missense	Exon 3 of 3	ENSP00000246139.5	Q99966-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181766 AF XY: 0.0000150

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097940 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363314

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54085

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40483

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842007

Other (OTH) AF: 0.0000217 AC: 1 AN: 46072

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.93
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.036
Sift	Benign	0.14	T
Sift4G	Benign	0.57	T
Polyphen		0.11	B
Vest4		0.061
MVP		0.93
MPC		0.35
ClinPred		0.13	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.31
Mutation Taster		=85/15	polymorphism

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: rs1174164523; hg19: chrX-71521803;