Variant X-49237077-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014008.5(CCDC22):c.51-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 112,625 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

CCDC22
NM_014008.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001216

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.230

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant X-49237077-C-T is Benign according to our data. Variant chrX-49237077-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3052729.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CCDC22	NM_014008.5 linkuse as main transcript	c.51-9C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000376227.4
CCDC22	XM_005272599.5 linkuse as main transcript	c.51-9C>T	splice_polypyrimidine_tract_variant, intron_variant
CCDC22	XR_430506.4 linkuse as main transcript	n.218-9C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CCDC22	ENST00000376227.4 linkuse as main transcript	c.51-9C>T	splice_polypyrimidine_tract_variant, intron_variant		1	NM_014008.5	P1
CCDC22	ENST00000490300.1 linkuse as main transcript	n.185C>T	non_coding_transcript_exon_variant	1/5	3
CCDC22	ENST00000496651.5 linkuse as main transcript	n.192-9C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112625

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34765

show subpopulations

Gnomad AFR

AF:

0.0000323

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000888

AC:

AN:

112625

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34765

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCDC22-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 09, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

Cadd

Benign

Dann

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.062

SpliceAI score (max)

0.12

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