Variant 22-23766101-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_213720.3(CHCHD10):c.409+27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,612,866 control chromosomes in the GnomAD database, including 535,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48697 hom., cov: 31)

Exomes 𝑓: 0.81 ( 487007 hom. )

Consequence

CHCHD10
NM_213720.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.95

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]

CHCHD10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 22-23766101-C-G is Benign according to our data. Variant chr22-23766101-C-G is described in ClinVar as [Benign]. Clinvar id is 1209687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHCHD10	NM_213720.3 linkuse as main transcript	c.409+27G>C	intron_variant	ENST00000484558.3
CHCHD10	NM_001301339.2 linkuse as main transcript	c.430+27G>C	intron_variant
CHCHD10	NR_125755.2 linkuse as main transcript	n.454+27G>C	intron_variant, non_coding_transcript_variant
CHCHD10	NR_125756.2 linkuse as main transcript	n.287+27G>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHCHD10	ENST00000484558.3 linkuse as main transcript	c.409+27G>C		intron_variant		1	NM_213720.3	P1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121268

AN:

151934

Hom.:

48681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.833

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.793

GnomAD3 exomes

AF:

0.781

AC:

193796

AN:

248202

Hom.:

76624

AF XY:

0.775

AC XY:

104306

AN XY:

134570

show subpopulations

Gnomad AFR exome

AF:

0.759

Gnomad AMR exome

AF:

0.812

Gnomad ASJ exome

AF:

0.840

Gnomad EAS exome

AF:

0.625

Gnomad SAS exome

AF:

0.608

Gnomad FIN exome

AF:

0.833

Gnomad NFE exome

AF:

0.831

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.814

AC:

1188716

AN:

1460814

Hom.:

487007

Cov.:

AF XY:

0.808

AC XY:

587139

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.818

Gnomad4 ASJ exome

AF:

0.838

Gnomad4 EAS exome

AF:

0.629

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.827

Gnomad4 NFE exome

AF:

0.837

Gnomad4 OTH exome

AF:

0.801

GnomAD4 genome

AF:

0.798

AC:

121324

AN:

152052

Hom.:

48697

Cov.:

AF XY:

0.793

AC XY:

58945

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.764

Gnomad4 AMR

AF:

0.832

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.592

Gnomad4 FIN

AF:

0.833

Gnomad4 NFE

AF:

0.831

Gnomad4 OTH

AF:

0.784

Alfa

AF:

0.789

Hom.:

5291

Bravo

AF:

0.798

Asia WGS

AF:

0.648

AC:

2255

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Frontotemporal dementia and/or amyotrophic lateral sclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Lower motor neuron syndrome with late-adult onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Autosomal dominant mitochondrial myopathy with exercise intolerance

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

0.039

Dann

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over