chrX-49235685-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_014008.5(CCDC22):​c.49A>G​(p.Thr17Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

CCDC22
NM_014008.5 missense, splice_region

Scores

5
12
Splicing: ADA: 0.9998
2

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.66
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
PP5
Variant X-49235685-A-G is Pathogenic according to our data. Variant chrX-49235685-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 218105.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.49A>G p.Thr17Ala missense_variant, splice_region_variant 1/17 ENST00000376227.4
CCDC22XM_005272599.5 linkuse as main transcriptc.49A>G p.Thr17Ala missense_variant, splice_region_variant 1/17
CCDC22XR_430506.4 linkuse as main transcriptn.216A>G splice_region_variant, non_coding_transcript_exon_variant 1/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC22ENST00000376227.4 linkuse as main transcriptc.49A>G p.Thr17Ala missense_variant, splice_region_variant 1/171 NM_014008.5 P1
CCDC22ENST00000496651.5 linkuse as main transcriptn.190A>G splice_region_variant, non_coding_transcript_exon_variant 1/63

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Ritscher-Schinzel syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 2012- -
Ritscher-Schinzel syndrome 1 Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.83
N
REVEL
Benign
0.13
Sift
Benign
0.23
T
Sift4G
Benign
0.099
T
Polyphen
0.90
P
Vest4
0.37
MutPred
0.45
Loss of loop (P = 0.1242);
MVP
0.79
MPC
3.1
ClinPred
0.92
D
GERP RS
3.7
Varity_R
0.22
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.99
SpliceAI score (max)
0.040
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: rs863225428; hg19: chrX-49092145; API