22-23765813-C-G

Position:

• chr22-23765813-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182520.3(C22orf15):​c.*81C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,532,650 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (79 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (80 hom.)
• Consequence: C22orf15 NM_182520.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.130

Genes affected

C22orf15 (HGNC:15558): (chromosome 22 open reading frame 15)

C22orf15 (HGNC:):

CHCHD10 (HGNC:15559): (coiled-coil-helix-coiled-coil-helix domain containing 10) This gene encodes a mitochondrial protein that is enriched at cristae junctions in the intermembrane space. It may play a role in cristae morphology maintenance or oxidative phosphorylation. Mutations in this gene cause frontotemporal dementia and/or amyotrophic lateral sclerosis-2. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 7 and 19. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-23765813-C-G is Benign according to our data. Variant chr22-23765813-C-G is described in ClinVar as [Benign]. Clinvar id is 1240465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C22orf15	NM_182520.3	c.*81C>G		3_prime_UTR_variant	6/6	ENST00000402217.8	NP_872326.2
CHCHD10	NM_213720.3	c.*194G>C		downstream_gene_variant		ENST00000484558.3	NP_998885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C22orf15	ENST00000402217.8	c.*81C>G		3_prime_UTR_variant	6/6	2	NM_182520.3	ENSP00000384965.4
CHCHD10	ENST00000484558.3	c.*194G>C		downstream_gene_variant		1	NM_213720.3	ENSP00000418428.3

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2636 AN: 152130 Hom.: 77 Cov.: 33

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00616

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00200 AC: 2767 AN: 1380402 Hom.: 80 Cov.: 30 AF XY: 0.00180 AC XY: 1224 AN XY: 681044

Gnomad4 AFR exome AF: 0.0630

Gnomad4 AMR exome AF: 0.00468

Gnomad4 ASJ exome AF: 0.00956

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000761

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.0174 AC: 2652 AN: 152248 Hom.: 79 Cov.: 33 AF XY: 0.0169 AC XY: 1257 AN XY: 74438

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00369 Hom.: 4

Bravo AF: 0.0201

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs73881809; hg19: chr22-24108000;