chrX-72301745-G-A

Variant names:

• chrX-72301745-G-A
• rs758955117
• NM_001144887.2:c.560C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001144887.2(CITED1):​c.560C>T​(p.Ala187Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000909 in 1,209,994 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 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: 𝑓 0.000018 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000098 (0 hom. 30 hem.)
• Consequence: CITED1 NM_001144887.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2652412).
• BS2: High Hemizygotes in GnomAdExome4 at 30 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.560C>T	p.Ala187Val	missense	Exon 3 of 3	NP_001138359.1	Q99966-1
	CITED1	NM_001144885.2		c.638C>T	p.Ala213Val	missense	Exon 4 of 4	NP_001138357.1	Q99966-2
	CITED1	NM_001144886.2		c.560C>T	p.Ala187Val	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.560C>T	p.Ala187Val	missense	Exon 3 of 3	ENSP00000499148.1	Q99966-1
	CITED1	ENST00000246139.9	TSL:1	c.560C>T	p.Ala187Val	missense	Exon 3 of 3	ENSP00000246139.5	Q99966-1
	CITED1	ENST00000373619.7	TSL:1	c.560C>T	p.Ala187Val	missense	Exon 3 of 3	ENSP00000362721.3	Q99966-1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112366 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000219 AC: 4 AN: 182756 AF XY: 0.0000149

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: 0.0000491

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000984 AC: 108 AN: 1097628 Hom.: 0 Cov.: 30 AF XY: 0.0000826 AC XY: 30 AN XY: 363018

African (AFR) AF: 0.0000379 AC: 1 AN: 26393

American (AMR) AF: 0.00 AC: 0 AN: 35178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19372

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 54087

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000126 AC: 106 AN: 841702

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

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112366 Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 1 AN XY: 34530

African (AFR) AF: 0.00 AC: 0 AN: 30904

American (AMR) AF: 0.00 AC: 0 AN: 10639

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3598

South Asian (SAS) AF: 0.00 AC: 0 AN: 2687

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53257

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.000142 Hom.: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

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	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.056	T
Polyphen		0.015	B
Vest4		0.39
MutPred		0.53		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.96
MPC		0.66
ClinPred		0.48	T
GERP RS		3.5
Varity_R		0.14
gMVP		0.40
Mutation Taster		=100/0	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: rs758955117; hg19: chrX-71521595; COSMIC: COSV104553797; COSMIC: COSV104553797;