Variant X-49237183-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_014008.5(CCDC22):c.148G>A(p.Gly50Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,210,824 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000021 ( 0 hom. 8 hem. )

Consequence

CCDC22
NM_014008.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

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:

CCDC22 (HGNC:):

CCDC22 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38305655).

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC22	NM_014008.5 linkuse as main transcript	c.148G>A	p.Gly50Ser	missense_variant	2/17	ENST00000376227.4	NP_054727.1	O60826A0A024QZ03
CCDC22	XM_005272599.5 linkuse as main transcript	c.148G>A	p.Gly50Ser	missense_variant	2/17		XP_005272656.1
CCDC22	XR_430506.4 linkuse as main transcript	n.315G>A		non_coding_transcript_exon_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC22	ENST00000376227.4 linkuse as main transcript	c.148G>A	p.Gly50Ser	missense_variant	2/17	1	NM_014008.5	ENSP00000365401.3	O60826
CCDC22	ENST00000490300.1 linkuse as main transcript	n.291G>A		non_coding_transcript_exon_variant	1/5	3
CCDC22	ENST00000496651.5 linkuse as main transcript	n.289G>A		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113089

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35225

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000548

AC:

AN:

182645

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1097735

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363131

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113089

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35225

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Ambry Genetics

Jul 14, 2024

The c.148G>A (p.G50S) alteration is located in exon 2 (coding exon 2) of the CCDC22 gene. This alteration results from a G to A substitution at nucleotide position 148, causing the glycine (G) at amino acid position 50 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

M_CAP

Benign

0.038

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.71

REVEL

Benign

0.19

Sift

Benign

0.16

Sift4G

Benign

0.13

Polyphen

0.95

Vest4

0.23

MutPred

0.64

Loss of catalytic residue at G50 (P = 0.0076);

MVP

0.74

MPC

1.8

ClinPred

0.73

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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