22-23765813-C-G

Variant names:

• chr22-23765813-C-G
• rs73881809
• NM_182520.3:c.*81C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

Genes affected

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

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]

CHCHD10 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant mitochondrial myopathy with exercise intolerance

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• frontotemporal dementia and/or amyotrophic lateral sclerosis 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• lower motor neuron syndrome with late-adult onset

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• frontotemporal dementia with motor neuron disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182520.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C22orf15	NM_182520.3	MANE Select	c.*81C>G		3_prime_UTR	Exon 6 of 6	NP_872326.2	Q8WYQ4-1
	C22orf15	NM_001331041.2		c.*59C>G		3_prime_UTR	Exon 6 of 6	NP_001317970.1	F8W7S3
	C22orf15	NM_001376903.1		c.*85C>G		3_prime_UTR	Exon 6 of 6	NP_001363832.1	Q8WYQ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C22orf15	ENST00000402217.8	TSL:2 MANE Select	c.*81C>G		3_prime_UTR	Exon 6 of 6	ENSP00000384965.4	Q8WYQ4-1
	C22orf15	ENST00000382821.3	TSL:1	c.*85C>G		3_prime_UTR	Exon 6 of 6	ENSP00000372271.3	Q8WYQ4-2
	C22orf15	ENST00000933353.1		c.*81C>G		3_prime_UTR	Exon 7 of 7	ENSP00000603412.1

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

African (AFR) AF: 0.0630 AC: 1959 AN: 31096

American (AMR) AF: 0.00468 AC: 163 AN: 34840

Ashkenazi Jewish (ASJ) AF: 0.00956 AC: 233 AN: 24380

East Asian (EAS) AF: 0.00 AC: 0 AN: 35618

South Asian (SAS) AF: 0.000193 AC: 15 AN: 77812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48866

Middle Eastern (MID) AF: 0.00322 AC: 18 AN: 5584

European-Non Finnish (NFE) AF: 0.0000761 AC: 81 AN: 1064866

Other (OTH) AF: 0.00520 AC: 298 AN: 57340

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

African (AFR) AF: 0.0597 AC: 2481 AN: 41542

American (AMR) AF: 0.00608 AC: 93 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68032

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.00369 Hom.: 4

Bravo AF: 0.0201

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73881809; hg19: chr22-24108000;