chrX-49237077-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

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 (no stars).

Frequency

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

Consequence

CCDC22
NM_014008.5 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00001216
2

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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 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 no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCDC22NM_014008.5 linkuse as main transcriptc.51-9C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000376227.4
CCDC22XM_005272599.5 linkuse as main transcriptc.51-9C>T splice_polypyrimidine_tract_variant, intron_variant
CCDC22XR_430506.4 linkuse as main transcriptn.218-9C>T splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC22ENST00000376227.4 linkuse as main transcriptc.51-9C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_014008.5 P1
CCDC22ENST00000490300.1 linkuse as main transcriptn.185C>T non_coding_transcript_exon_variant 1/53
CCDC22ENST00000496651.5 linkuse as main transcriptn.192-9C>T splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000888
AC:
1
AN:
112625
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
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.:
30
GnomAD4 genome
AF:
0.00000888
AC:
1
AN:
112625
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
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.:
0
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 submitterclinical testingPreventionGenetics, part of Exact SciencesJan 09, 2023This 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
12
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.

Other links and lift over

dbSNP: rs1443511548; hg19: chrX-49093544; API