X-72301959-C-T

Variant names:

• chrX-72301959-C-T
• rs774180523
• NM_001144887.2:c.346G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001144887.2(CITED1):​c.346G>A​(p.Gly116Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,210,630 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000021 (0 hom. 10 hem.)
• Consequence: CITED1 NM_001144887.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.161
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12839898).
• BS2: High Hemizygotes in GnomAdExome4 at 10 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.346G>A	p.Gly116Arg	missense	Exon 3 of 3	NP_001138359.1	Q99966-1
	CITED1	NM_001144885.2		c.424G>A	p.Gly142Arg	missense	Exon 4 of 4	NP_001138357.1	Q99966-2
	CITED1	NM_001144886.2		c.346G>A	p.Gly116Arg	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.346G>A	p.Gly116Arg	missense	Exon 3 of 3	ENSP00000499148.1	Q99966-1
	ENSG00000285547	ENST00000648922.1		c.1522G>A	p.Gly508Arg	missense	Exon 12 of 12	ENSP00000497072.1	A0A3B3IRV1
	CITED1	ENST00000246139.9	TSL:1	c.346G>A	p.Gly116Arg	missense	Exon 3 of 3	ENSP00000246139.5	Q99966-1

Frequencies

GnomAD3 genomes AF: 0.00000886 AC: 1 AN: 112819 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: 0.0000187

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000607 AC: 11 AN: 181328 AF XY: 0.0000605

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000248

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1097811 Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 10 AN XY: 363207

African (AFR) AF: 0.00 AC: 0 AN: 26390

American (AMR) AF: 0.000114 AC: 4 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19374

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30187

South Asian (SAS) AF: 0.0000740 AC: 4 AN: 54066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40456

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

European-Non Finnish (NFE) AF: 0.0000166 AC: 14 AN: 841959

Other (OTH) AF: 0.00 AC: 0 AN: 46071

GnomAD4 genome AF: 0.00000886 AC: 1 AN: 112819 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34959

African (AFR) AF: 0.00 AC: 0 AN: 31012

American (AMR) AF: 0.00 AC: 0 AN: 10761

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3596

South Asian (SAS) AF: 0.00 AC: 0 AN: 2740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6268

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

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53348

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000741 AC: 9

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	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.16
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.030	D
Sift4G	Benign	0.22	T
Polyphen		0.18	B
Vest4		0.039
MutPred		0.60		Loss of catalytic residue at P112 (P = 0.0722)
MVP		0.97
MPC		0.68
ClinPred		0.066	T
GERP RS		3.9
Varity_R		0.096
gMVP		0.44
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: rs774180523; hg19: chrX-71521809;