chr22-23765999-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_213720.3(CHCHD10):c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,613,386 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 0.00034 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 0 hom. )
Consequence
CHCHD10
NM_213720.3 3_prime_UTR
NM_213720.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.76
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 22-23765999-C-T is Benign according to our data. Variant chr22-23765999-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046372.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000342 (52/152168) while in subpopulation NFE AF= 0.000706 (48/68008). AF 95% confidence interval is 0.000547. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 52 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHCHD10 | NM_213720.3 | c.*8G>A | 3_prime_UTR_variant | 4/4 | ENST00000484558.3 | ||
CHCHD10 | NM_001301339.2 | c.*8G>A | 3_prime_UTR_variant | 4/4 | |||
CHCHD10 | NR_125755.2 | n.482G>A | non_coding_transcript_exon_variant | 4/4 | |||
CHCHD10 | NR_125756.2 | n.315G>A | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHCHD10 | ENST00000484558.3 | c.*8G>A | 3_prime_UTR_variant | 4/4 | 1 | NM_213720.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152050Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000181 AC: 45AN: 248296Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 134696
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GnomAD4 exome AF: 0.000335 AC: 490AN: 1461218Hom.: 0 Cov.: 32 AF XY: 0.000333 AC XY: 242AN XY: 726892
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CHCHD10-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 22, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at