22-23766101-C-G

Variant names:

• chr22-23766101-C-G
• rs140182
• NM_213720.3:c.409+27G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213720.3(CHCHD10):​c.409+27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,612,866 control chromosomes in the GnomAD database, including 535,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48697 hom., cov: 31)
  • Exomes 𝑓: 0.81 (487007 hom.)
• Consequence: CHCHD10 NM_213720.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.95
• Publications: 15 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-23766101-C-G is Benign according to our data. Variant chr22-23766101-C-G is described in ClinVar as Benign. ClinVar VariationId is 1209687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213720.3. 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
	CHCHD10	NM_213720.3	MANE Select	c.409+27G>C		intron	N/A	NP_998885.1	Q8WYQ3
	CHCHD10	NM_001301339.2		c.430+27G>C		intron	N/A	NP_001288268.1	B5MBW9
	CHCHD10	NR_125755.2		n.454+27G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHCHD10	ENST00000484558.3	TSL:1 MANE Select	c.409+27G>C		intron	N/A	ENSP00000418428.3	Q8WYQ3
	CHCHD10	ENST00000878118.1		c.472+27G>C		intron	N/A	ENSP00000548177.1
	CHCHD10	ENST00000878120.1		c.409+27G>C		intron	N/A	ENSP00000548179.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121268 AN: 151934 Hom.: 48681 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.793

GnomAD2 exomes AF: 0.781 AC: 193796 AN: 248202 AF XY: 0.775

Gnomad AFR exome AF: 0.759

Gnomad AMR exome AF: 0.812

Gnomad ASJ exome AF: 0.840

Gnomad EAS exome AF: 0.625

Gnomad FIN exome AF: 0.833

Gnomad NFE exome AF: 0.831

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.814 AC: 1188716 AN: 1460814 Hom.: 487007 Cov.: 69 AF XY: 0.808 AC XY: 587139 AN XY: 726624

African (AFR) AF: 0.758 AC: 25364 AN: 33456

American (AMR) AF: 0.818 AC: 36436 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 21889 AN: 26108

East Asian (EAS) AF: 0.629 AC: 24944 AN: 39650

South Asian (SAS) AF: 0.613 AC: 52791 AN: 86104

European-Finnish (FIN) AF: 0.827 AC: 44056 AN: 53240

Middle Eastern (MID) AF: 0.765 AC: 4413 AN: 5766

European-Non Finnish (NFE) AF: 0.837 AC: 930449 AN: 1111558

Other (OTH) AF: 0.801 AC: 48374 AN: 60362

GnomAD4 genome AF: 0.798 AC: 121324 AN: 152052 Hom.: 48697 Cov.: 31 AF XY: 0.793 AC XY: 58945 AN XY: 74332

African (AFR) AF: 0.764 AC: 31662 AN: 41458

American (AMR) AF: 0.832 AC: 12720 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2917 AN: 3472

East Asian (EAS) AF: 0.636 AC: 3282 AN: 5158

South Asian (SAS) AF: 0.592 AC: 2846 AN: 4808

European-Finnish (FIN) AF: 0.833 AC: 8826 AN: 10596

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56487 AN: 67956

Other (OTH) AF: 0.784 AC: 1653 AN: 2108

Alfa AF: 0.789 Hom.: 5291

Bravo AF: 0.798

Asia WGS AF: 0.648 AC: 2255 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant mitochondrial myopathy with exercise intolerance (1)
-	-	1	Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (1)
-	-	1	Lower motor neuron syndrome with late-adult onset (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.039
DANN	Benign	0.74
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs140182; hg19: chr22-24108288; COSMIC: COSV59418049; COSMIC: COSV59418049;