rs774466084

Variant names:

• chrX-72302842-C-G
• rs774466084
• NM_001144887.2:c.28G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-72302842-C-G
• chrX-72302842-C-T

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.28G>C​(p.Asp10His) 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 1,096,768 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D10N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: CITED1 NM_001144887.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• 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=0.22294462).

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.28G>C	p.Asp10His	missense	Exon 2 of 3	NP_001138359.1	Q99966-1
	CITED1	NM_001144885.2		c.106G>C	p.Asp36His	missense	Exon 3 of 4	NP_001138357.1	Q99966-2
	CITED1	NM_001144886.2		c.28G>C	p.Asp10His	missense	Exon 2 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.28G>C	p.Asp10His	missense	Exon 2 of 3	ENSP00000499148.1	Q99966-1
	ENSG00000285547	ENST00000648922.1		c.1204G>C	p.Asp402His	missense	Exon 11 of 12	ENSP00000497072.1	A0A3B3IRV1
	CITED1	ENST00000246139.9	TSL:1	c.28G>C	p.Asp10His	missense	Exon 2 of 3	ENSP00000246139.5	Q99966-1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 180164 AF XY: 0.0000154

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: 0.0000125

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096768 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362194

African (AFR) AF: 0.00 AC: 0 AN: 26382

American (AMR) AF: 0.00 AC: 0 AN: 35147

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 53891

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841190

Other (OTH) AF: 0.0000217 AC: 1 AN: 46038

GnomAD4 genome Cov.: 25

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.21		Gain of MoRF binding (P = 0.0342)
MVP		0.92
MPC		0.79
ClinPred		0.56	D
GERP RS		4.1
PromoterAI		0.0028	Neutral
Varity_R		0.32
gMVP		0.47
Mutation Taster		=99/1	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: rs774466084; hg19: chrX-71522692;