X-49250467-C-G

Variant names:

• chrX-49250467-C-G
• rs181219991
• NM_014008.5:c.*206C>G

Variant summary

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

The NM_014008.5(CCDC22):​c.*206C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 497,360 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., 3 hem., cov: 24)
  • Exomes 𝑓: 0.000034 (0 hom. 5 hem.)
• Consequence: CCDC22 NM_014008.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.490
• Publications: 0 publications found

Genes affected

CCDC22 (HGNC:28909): (coiled-coil domain containing 22) This gene encodes a protein containing a coiled-coil domain. The encoded protein functions in the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) by interacting with COMMD (copper metabolism Murr1 domain-containing) proteins. The mouse orthologous protein has been shown to bind copines, which are calcium-dependent, membrane-binding proteins that may function in calcium signaling. This human gene has been identified as a novel candidate gene for syndromic X-linked intellectual disability. [provided by RefSeq, Aug 2013]

FOXP3 (HGNC:6106): (forkhead box P3) The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FOXP3 Gene-Disease associations (from GenCC):

• immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.038).
• BS2: High Hemizygotes in GnomAd4 at 3 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014008.5. 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
	CCDC22	NM_014008.5	MANE Select	c.*206C>G		3_prime_UTR	Exon 17 of 17	NP_054727.1	O60826
	FOXP3	NM_014009.4	MANE Select	c.*867G>C		3_prime_UTR	Exon 12 of 12	NP_054728.2
	FOXP3	NM_001114377.2		c.*867G>C		3_prime_UTR	Exon 11 of 11	NP_001107849.1	Q9BZS1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.*206C>G		3_prime_UTR	Exon 17 of 17	ENSP00000365401.3	O60826
	FOXP3	ENST00000376207.10	TSL:1 MANE Select	c.*867G>C		3_prime_UTR	Exon 12 of 12	ENSP00000365380.4	Q9BZS1-1
	CCDC22	ENST00000960401.1		c.*206C>G		3_prime_UTR	Exon 17 of 17	ENSP00000630460.1

Frequencies

GnomAD3 genomes AF: 0.0000979 AC: 11 AN: 112316 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000938

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: 0.0000428 AC: 4 AN: 93393 AF XY: 0.0000290

Gnomad AFR exome AF: 0.000416

Gnomad AMR exome AF: 0.000105

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: 0.0000338 AC: 13 AN: 385044 Hom.: 0 Cov.: 0 AF XY: 0.0000367 AC XY: 5 AN XY: 136058

African (AFR) AF: 0.000739 AC: 9 AN: 12183

American (AMR) AF: 0.0000755 AC: 2 AN: 26474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14135

East Asian (EAS) AF: 0.00 AC: 0 AN: 22910

South Asian (SAS) AF: 0.00 AC: 0 AN: 37018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23951

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2807

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 223421

Other (OTH) AF: 0.0000903 AC: 2 AN: 22145

GnomAD4 genome AF: 0.0000979 AC: 11 AN: 112316 Hom.: 0 Cov.: 24 AF XY: 0.0000870 AC XY: 3 AN XY: 34500

African (AFR) AF: 0.000324 AC: 10 AN: 30904

American (AMR) AF: 0.0000938 AC: 1 AN: 10664

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6143

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53198

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000140

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
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		0.49
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: rs181219991; hg19: chrX-49106928;