22-23767401-C-T

Position:

chr22-23767401-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_213720.3(CHCHD10):c.234G>A(p.Ser78Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,608,354 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 5 hom., cov: 33)

Exomes 𝑓: 0.011 ( 84 hom. )

Consequence

CHCHD10
NM_213720.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 22-23767401-C-T is Benign according to our data. Variant chr22-23767401-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767401-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.35 with no splicing effect.

BS2

High AC in GnomAd4 at 1113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHCHD10	NM_213720.3 link	c.234G>A	p.Ser78Ser	synonymous_variant	2/4	ENST00000484558.3	NP_998885.1	Q8WYQ3
CHCHD10	NM_001301339.2 link	c.234G>A	p.Ser78Ser	synonymous_variant	2/4		NP_001288268.1	Q8WYQ3B5MBW9
CHCHD10	NR_125755.2 link	n.279G>A		non_coding_transcript_exon_variant	2/4
CHCHD10	NR_125756.2 link	n.139+433G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHCHD10	ENST00000484558.3 link	c.234G>A	p.Ser78Ser	synonymous_variant	2/4	1	NM_213720.3	ENSP00000418428.3	Q8WYQ3
CHCHD10	ENST00000401675.7 link	c.234G>A	p.Ser78Ser	synonymous_variant	2/4	5		ENSP00000384973.3	B5MBW9
CHCHD10	ENST00000520222.1 link	c.41+433G>A		intron_variant		3		ENSP00000430042.1	E5RH03
CHCHD10	ENST00000517886.1 link	n.181G>A		non_coding_transcript_exon_variant	2/4	3		ENSP00000429976.1	E5RGN4

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1113

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00760

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00641

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00740

AC:

1744

AN:

235754

Hom.:

AF XY:

0.00753

AC XY:

977

AN XY:

129802

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.00436

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.00751

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.00950

GnomAD4 exome

AF:

0.0106

AC:

15501

AN:

1456140

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

7562

AN XY:

724162

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00442

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00264

Gnomad4 FIN exome

AF:

0.00789

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00813

GnomAD4 genome

AF:

0.00731

AC:

1113

AN:

152214

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00759

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00641

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00772

Hom.:

Bravo

AF:

0.00677

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 28, 2018	This variant is associated with the following publications: (PMID: 27095681, 25726362) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CHCHD10: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

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. -

CHCHD10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2019

This variant is classified as 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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.4

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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