X-49246763-A-G

Variant names:

• chrX-49246763-A-G
• rs2294020
• NM_014008.5:c.747A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_014008.5(CCDC22):​c.747A>G​(p.Gln249Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (15335 hom., 20559 hem., cov: 24)
  • Exomes 𝑓: 0.69 (175068 hom. 236243 hem.)
  • Failed GnomAD Quality Control
• Consequence: CCDC22 NM_014008.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.164

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant X-49246763-A-G is Benign according to our data. Variant chrX-49246763-A-G is described in ClinVar as [Benign]. Clinvar id is 769177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.164 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 7 of 17	ENST00000376227.4	NP_054727.1
CCDC22	XM_005272599.5	c.744A>G	p.Gln248Gln	synonymous_variant	Exon 7 of 17		XP_005272656.1
CCDC22	XR_430506.4	n.914A>G		non_coding_transcript_exon_variant	Exon 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 7 of 17	1	NM_014008.5	ENSP00000365401.3

Frequencies

GnomAD3 genomes AF: 0.609 AC: 68218 AN: 111928 Hom.: 15335 Cov.: 24 AF XY: 0.601 AC XY: 20517 AN XY: 34116

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.620

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.694 AC: 734524 AN: 1059082 Hom.: 175068 Cov.: 38 AF XY: 0.698 AC XY: 236243 AN XY: 338646

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.722

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.609 AC: 68250 AN: 111978 Hom.: 15335 Cov.: 24 AF XY: 0.602 AC XY: 20559 AN XY: 34176

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.621

Alfa AF: 0.681 Hom.: 20982

Bravo AF: 0.590

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2294020; hg19: chrX-49103224;