rs730880031
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_213720.3(CHCHD10):c.197G>T(p.Gly66Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,452,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CHCHD10
NM_213720.3 missense
NM_213720.3 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 5.76
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833
PP5
Variant 22-23767438-C-A is Pathogenic according to our data. Variant chr22-23767438-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 180221.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23767438-C-A is described in UniProt as null.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHCHD10 | NM_213720.3 | c.197G>T | p.Gly66Val | missense_variant | 2/4 | ENST00000484558.3 | NP_998885.1 | |
CHCHD10 | NM_001301339.2 | c.197G>T | p.Gly66Val | missense_variant | 2/4 | NP_001288268.1 | ||
CHCHD10 | NR_125755.2 | n.242G>T | non_coding_transcript_exon_variant | 2/4 | ||||
CHCHD10 | NR_125756.2 | n.139+396G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHCHD10 | ENST00000484558.3 | c.197G>T | p.Gly66Val | missense_variant | 2/4 | 1 | NM_213720.3 | ENSP00000418428.3 | ||
CHCHD10 | ENST00000401675.7 | c.197G>T | p.Gly66Val | missense_variant | 2/4 | 5 | ENSP00000384973.3 | |||
CHCHD10 | ENST00000520222.1 | c.41+396G>T | intron_variant | 3 | ENSP00000430042.1 | |||||
CHCHD10 | ENST00000517886.1 | n.144G>T | non_coding_transcript_exon_variant | 2/4 | 3 | ENSP00000429976.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000176 AC: 4AN: 226942Hom.: 0 AF XY: 0.00000798 AC XY: 1AN XY: 125306
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1452808Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 722274
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lower motor neuron syndrome with late-adult onset Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2015 | - - |
Likely pathogenic, no assertion criteria provided | provider interpretation | Solve-RD Consortium | Jun 01, 2022 | Variant confirmed as disease-causing by referring clinical team - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics Laboratory, Skane University Hospital Lund | Apr 28, 2023 | - - |
Autosomal dominant mitochondrial myopathy with exercise intolerance Other:1
not provided, no classification provided | literature only | GeneReviews | - | Founder variant in Finnish population, associated with late-onset SMN (spinal motor neuropathy) or SMAJ (spinal muscular atrophy, Jokela type) and axonal CMT (Charcot-Marie-Tooth) disease - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MutPred
Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP
MPC
1.6
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at