rs374353973
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_213720.3(CHCHD10):āc.274G>Cā(p.Ala92Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0015 ( 0 hom., cov: 22)
Exomes š: 0.098 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CHCHD10
NM_213720.3 missense
NM_213720.3 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -0.886
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0025873482).
BP6
Variant 22-23766263-C-G is Benign according to our data. Variant chr22-23766263-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1259100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23766263-C-G is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHCHD10 | NM_213720.3 | c.274G>C | p.Ala92Pro | missense_variant | 3/4 | ENST00000484558.3 | NP_998885.1 | |
CHCHD10 | NM_001301339.2 | c.295G>C | p.Ala99Pro | missense_variant | 3/4 | NP_001288268.1 | ||
CHCHD10 | NR_125755.2 | n.319G>C | non_coding_transcript_exon_variant | 3/4 | ||||
CHCHD10 | NR_125756.2 | n.152G>C | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHCHD10 | ENST00000484558.3 | c.274G>C | p.Ala92Pro | missense_variant | 3/4 | 1 | NM_213720.3 | ENSP00000418428.3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 116AN: 79090Hom.: 0 Cov.: 22 FAILED QC
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GnomAD3 exomes AF: 0.0831 AC: 6718AN: 80812Hom.: 0 AF XY: 0.0786 AC XY: 3548AN XY: 45124
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0980 AC: 63389AN: 646636Hom.: 0 Cov.: 24 AF XY: 0.0985 AC XY: 31896AN XY: 323752
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00147 AC: 116AN: 79100Hom.: 0 Cov.: 22 AF XY: 0.00147 AC XY: 56AN XY: 38030
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 20, 2019 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0010
.;B
Vest4
MutPred
0.30
.;Gain of glycosylation at A92 (P = 0.0011);
MPC
0.66
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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