rs184896758

Variant names:

• chrX-49248262-C-G
• rs184896758
• NM_014008.5:c.1164C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-49248262-C-G
• chrX-49248262-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014008.5(CCDC22):​c.1164C>G​(p.Arg388Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,059,291 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. Synonymous variant affecting the same amino acid position (i.e. R388R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: CCDC22 NM_014008.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Ritscher-Schinzel syndrome 2

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Ritscher-Schinzel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=0.279 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5	c.1164C>G	p.Arg388Arg	synonymous_variant	Exon 10 of 17	ENST00000376227.4	NP_054727.1
CCDC22	XM_005272599.5	c.1161C>G	p.Arg387Arg	synonymous_variant	Exon 10 of 17		XP_005272656.1
CCDC22	XR_430506.4	n.1327C>G		non_coding_transcript_exon_variant	Exon 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4	c.1164C>G	p.Arg388Arg	synonymous_variant	Exon 10 of 17	1	NM_014008.5	ENSP00000365401.3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000283 AC: 3 AN: 1059291 Hom.: 0 Cov.: 33 AF XY: 0.00000290 AC XY: 1 AN XY: 344339

African (AFR) AF: 0.00 AC: 0 AN: 25406

American (AMR) AF: 0.00 AC: 0 AN: 34031

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18075

East Asian (EAS) AF: 0.00 AC: 0 AN: 27413

South Asian (SAS) AF: 0.00 AC: 0 AN: 53603

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34737

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3655

European-Non Finnish (NFE) AF: 0.00000366 AC: 3 AN: 818685

Other (OTH) AF: 0.00 AC: 0 AN: 43686

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		0.28

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

Other links and lift over

dbSNP: rs184896758; hg19: chrX-49104723;