rs754492535

Variant names:

• chr22-23766045-C-G
• rs754492535
• NM_213720.3:c.410-19G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-23766045-C-G
• chr22-23766045-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_213720.3(CHCHD10):​c.410-19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CHCHD10 NM_213720.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 22-23766045-C-G is Benign according to our data. Variant chr22-23766045-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1562244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 15 AD gene.

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.410-19G>C		intron	N/A	NP_998885.1	Q8WYQ3
	CHCHD10	NM_001301339.2		c.431-19G>C		intron	N/A	NP_001288268.1	B5MBW9
	CHCHD10	NR_125755.2		n.455-19G>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.410-19G>C		intron	N/A	ENSP00000418428.3	Q8WYQ3
	CHCHD10	ENST00000878120.1		c.415G>C	p.Ala139Pro	missense	Exon 4 of 4	ENSP00000548179.1
	CHCHD10	ENST00000878118.1		c.473-19G>C		intron	N/A	ENSP00000548177.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000242 AC: 6 AN: 247936 AF XY: 0.0000223

Gnomad AFR exome AF: 0.0000630

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461320 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726932

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000895 AC: 4 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74310

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.000851 AC: 13 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000110

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Lower motor neuron syndrome with late-adult onset;C4014648:Frontotemporal dementia and/or amyotrophic lateral sclerosis 2;C4015513:Autosomal dominant mitochondrial myopathy with exercise intolerance (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.6
DANN	Benign	0.86
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs754492535; hg19: chr22-24108232;