rs1383516253

Variant names:

• chrX-72302148-T-A
• rs1383516253
• NM_001144887.2:c.157A>T

Variant summary

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

The NM_001144887.2(CITED1):​c.157A>T​(p.Asn53Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000418 in 1,195,094 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N53S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000037 (0 hom. 0 hem.)
• Consequence: CITED1 NM_001144887.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.157A>T	p.Asn53Tyr	missense	Exon 3 of 3	NP_001138359.1	Q99966-1
	CITED1	NM_001144885.2		c.235A>T	p.Asn79Tyr	missense	Exon 4 of 4	NP_001138357.1	Q99966-2
	CITED1	NM_001144886.2		c.157A>T	p.Asn53Tyr	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.157A>T	p.Asn53Tyr	missense	Exon 3 of 3	ENSP00000499148.1	Q99966-1
	ENSG00000285547	ENST00000648922.1		c.1333A>T	p.Asn445Tyr	missense	Exon 12 of 12	ENSP00000497072.1	A0A3B3IRV1
	CITED1	ENST00000246139.9	TSL:1	c.157A>T	p.Asn53Tyr	missense	Exon 3 of 3	ENSP00000246139.5	Q99966-1

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112320 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000937

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000668 AC: 1 AN: 149637 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000414

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: 0.00

GnomAD4 exome AF: 0.00000369 AC: 4 AN: 1082774 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 353210

African (AFR) AF: 0.00 AC: 0 AN: 26112

American (AMR) AF: 0.0000915 AC: 3 AN: 32774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19114

East Asian (EAS) AF: 0.00 AC: 0 AN: 29575

South Asian (SAS) AF: 0.00 AC: 0 AN: 51934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4117

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833948

Other (OTH) AF: 0.0000219 AC: 1 AN: 45568

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112320 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34474

African (AFR) AF: 0.00 AC: 0 AN: 30944

American (AMR) AF: 0.0000937 AC: 1 AN: 10678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2685

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6183

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53175

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.17
BayesDel_addAF	Benign	0.0065	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.1
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.59		Loss of disorder (P = 0.0756)
MVP		0.90
MPC		0.75
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.27
gMVP		0.40
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1383516253; hg19: chrX-71521998;