rs9153

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_213720.3(CHCHD10):c.312C>T(p.Tyr104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,577,154 control chromosomes in the GnomAD database, including 506,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48248 hom., cov: 24)

Exomes 𝑓: 0.80 ( 458096 hom. )

Consequence

CHCHD10
NM_213720.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0940

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.019759E-6).

BP6

Variant 22-23766225-G-A is Benign according to our data. Variant chr22-23766225-G-A is described in ClinVar as [Benign]. Clinvar id is 379953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23766225-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.094 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHCHD10	NM_213720.3 linkuse as main transcript	c.312C>T	p.Tyr104=	synonymous_variant	3/4	ENST00000484558.3
CHCHD10	NM_001301339.2 linkuse as main transcript	c.333C>T	p.Tyr111=	synonymous_variant	3/4
CHCHD10	NR_125755.2 linkuse as main transcript	n.357C>T		non_coding_transcript_exon_variant	3/4
CHCHD10	NR_125756.2 linkuse as main transcript	n.190C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHCHD10	ENST00000484558.3 linkuse as main transcript	c.312C>T	p.Tyr104=	synonymous_variant	3/4	1	NM_213720.3	P1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

119979

AN:

150144

Hom.:

48232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.751

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.834

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.793

GnomAD3 exomes

AF:

0.779

AC:

171489

AN:

220022

Hom.:

67426

AF XY:

0.773

AC XY:

91957

AN XY:

118930

show subpopulations

Gnomad AFR exome

AF:

0.759

Gnomad AMR exome

AF:

0.811

Gnomad ASJ exome

AF:

0.840

Gnomad EAS exome

AF:

0.626

Gnomad SAS exome

AF:

0.608

Gnomad FIN exome

AF:

0.833

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.799

GnomAD4 exome

AF:

0.801

AC:

1143599

AN:

1426896

Hom.:

458096

Cov.:

AF XY:

0.797

AC XY:

564634

AN XY:

708842

show subpopulations

Gnomad4 AFR exome

AF:

0.747

Gnomad4 AMR exome

AF:

0.816

Gnomad4 ASJ exome

AF:

0.833

Gnomad4 EAS exome

AF:

0.627

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.827

Gnomad4 NFE exome

AF:

0.822

Gnomad4 OTH exome

AF:

0.792

GnomAD4 genome

AF:

0.799

AC:

120034

AN:

150258

Hom.:

48248

Cov.:

AF XY:

0.794

AC XY:

58159

AN XY:

73238

show subpopulations

Gnomad4 AFR

AF:

0.765

Gnomad4 AMR

AF:

0.832

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.638

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.834

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.785

Alfa

AF:

0.816

Hom.:

22072

Bravo

AF:

0.798

TwinsUK

AF:

0.848

AC:

3143

ALSPAC

AF:

0.848

AC:

3269

ESP6500AA

AF:

0.751

AC:

3311

ESP6500EA

AF:

0.832

AC:

7159

ExAC

AF:

0.758

AC:

91429

Asia WGS

AF:

0.646

AC:

2245

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 03, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Lower motor neuron syndrome with late-adult onset

Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

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;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

Invitae

Feb 01, 2024

- -

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_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.6

DANN

Benign

0.95

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

P;P;P

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.49

Vest4

0.15

ClinPred

0.070

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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