X-49237061-C-T

Position:

• chrX-49237061-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014008.5(CCDC22):​c.51-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 111,579 control chromosomes in the GnomAD database, including 9,550 homozygotes. There are 14,085 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.43 (9550 hom., 14085 hem., cov: 24)
  • Exomes 𝑓: 0.57 (126793 hom. 200355 hem.)
  • Failed GnomAD Quality Control
• Consequence: CCDC22 NM_014008.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC22	NM_014008.5	c.51-25C>T		intron_variant		ENST00000376227.4	NP_054727.1
CCDC22	XM_005272599.5	c.51-25C>T		intron_variant			XP_005272656.1
CCDC22	XR_430506.4	n.218-25C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4	c.51-25C>T		intron_variant		1	NM_014008.5	ENSP00000365401	P1
CCDC22	ENST00000490300.1	n.169C>T		non_coding_transcript_exon_variant	1/5	3
CCDC22	ENST00000496651.5	n.192-25C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 47752 AN: 111523 Hom.: 9557 Cov.: 24 AF XY: 0.417 AC XY: 14072 AN XY: 33739

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.475

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.574 AC: 619307 AN: 1078301 Hom.: 126793 Cov.: 27 AF XY: 0.576 AC XY: 200355 AN XY: 347585

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.428 AC: 47739 AN: 111579 Hom.: 9550 Cov.: 24 AF XY: 0.417 AC XY: 14085 AN XY: 33805

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.473

Alfa AF: 0.561 Hom.: 19767

Bravo AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.077
BranchPoint Hunter		3.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294016; hg19: chrX-49093528;