chr22-23767827-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_213720.3(CHCHD10):​c.41+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,541,748 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

CHCHD10
NM_213720.3 splice_region, intron

Scores

2
Splicing: ADA: 0.0001517
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.12
Variant links:
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 -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 22-23767827-C-T is Benign according to our data. Variant chr22-23767827-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767827-C-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 215 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHCHD10NM_213720.3 linkc.41+7G>A splice_region_variant, intron_variant Intron 1 of 3 ENST00000484558.3 NP_998885.1 Q8WYQ3
CHCHD10NM_001301339.2 linkc.41+7G>A splice_region_variant, intron_variant Intron 1 of 3 NP_001288268.1 Q8WYQ3B5MBW9
CHCHD10NR_125755.2 linkn.139+7G>A splice_region_variant, intron_variant Intron 1 of 3
CHCHD10NR_125756.2 linkn.139+7G>A splice_region_variant, intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHCHD10ENST00000484558.3 linkc.41+7G>A splice_region_variant, intron_variant Intron 1 of 3 1 NM_213720.3 ENSP00000418428.3 Q8WYQ3
CHCHD10ENST00000401675.7 linkc.41+7G>A splice_region_variant, intron_variant Intron 1 of 3 5 ENSP00000384973.3 B5MBW9
CHCHD10ENST00000520222.1 linkc.41+7G>A splice_region_variant, intron_variant Intron 1 of 2 3 ENSP00000430042.1 E5RH03
CHCHD10ENST00000517886.1 linkn.41+7G>A splice_region_variant, intron_variant Intron 1 of 3 3 ENSP00000429976.1 E5RGN4

Frequencies

GnomAD3 genomes
AF:
0.00141
AC:
215
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00279
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00103
AC:
170
AN:
164424
Hom.:
1
AF XY:
0.00102
AC XY:
95
AN XY:
92784
show subpopulations
Gnomad AFR exome
AF:
0.000521
Gnomad AMR exome
AF:
0.000424
Gnomad ASJ exome
AF:
0.00143
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000568
Gnomad NFE exome
AF:
0.00188
Gnomad OTH exome
AF:
0.00270
GnomAD4 exome
AF:
0.00223
AC:
3092
AN:
1389578
Hom.:
8
Cov.:
30
AF XY:
0.00212
AC XY:
1460
AN XY:
688540
show subpopulations
Gnomad4 AFR exome
AF:
0.000175
Gnomad4 AMR exome
AF:
0.000428
Gnomad4 ASJ exome
AF:
0.00156
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000127
Gnomad4 FIN exome
AF:
0.000261
Gnomad4 NFE exome
AF:
0.00267
Gnomad4 OTH exome
AF:
0.00242
GnomAD4 genome
AF:
0.00141
AC:
215
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.00113
AC XY:
84
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00279
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.00188
Hom.:
2
Bravo
AF:
0.00122

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Jul 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

CHCHD10: BP4, BS1, BS2 -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

CHCHD10-related disorder Benign:1
Jun 05, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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). -

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 Benign:1
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.76
DANN
Benign
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00015
dbscSNV1_RF
Benign
0.0040
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141526972; hg19: chr22-24110014; API