Variant X-49250467-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.490

Variant links:

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]

CCDC22 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BS2

High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CCDC22	NM_014008.5 linkuse as main transcript	c.*206C>G	3_prime_UTR_variant	17/17	ENST00000376227.4
FOXP3	NM_014009.4 linkuse as main transcript	c.*867G>C	3_prime_UTR_variant	12/12	ENST00000376207.10
FOXP3	NM_001114377.2 linkuse as main transcript	c.*867G>C	3_prime_UTR_variant	11/11
CCDC22	XM_005272599.5 linkuse as main transcript	c.*206C>G	3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP3	ENST00000376207.10 linkuse as main transcript	c.*867G>C		3_prime_UTR_variant	12/12	1	NM_014009.4	P1	Q9BZS1-1
CCDC22	ENST00000376227.4 linkuse as main transcript	c.*206C>G		3_prime_UTR_variant	17/17	1	NM_014008.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000979

AC:

AN:

112316

Hom.:

Cov.:

AF XY:

0.0000870

AC XY:

AN XY:

34500

show subpopulations

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

GnomAD3 exomes

AF:

0.0000428

AC:

AN:

93393

Hom.:

AF XY:

0.0000290

AC XY:

AN XY:

34493

show subpopulations

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 SAS 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:

AN:

385044

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

136058

show subpopulations

Gnomad4 AFR exome

AF:

0.000739

Gnomad4 AMR exome

AF:

0.0000755

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000903

GnomAD4 genome

AF:

0.0000979

AC:

AN:

112316

Hom.:

Cov.:

AF XY:

0.0000870

AC XY:

AN XY:

34500

show subpopulations

Gnomad4 AFR

AF:

0.000324

Gnomad4 AMR

AF:

0.0000938

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000140

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

Cadd

Benign

7.5

Dann

Benign

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over