chr22-23766131-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_213720.3(CHCHD10):c.406C>T(p.His136Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. H136H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHCHD10
NM_213720.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.20

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant mitochondrial myopathy with exercise intolerance
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
frontotemporal dementia and/or amyotrophic lateral sclerosis 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
lower motor neuron syndrome with late-adult onset
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
frontotemporal dementia with motor neuron disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHCHD10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06280354).

BP6

Variant 22-23766131-G-A is Benign according to our data. Variant chr22-23766131-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3144058.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213720.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHCHD10	NM_213720.3	MANE Select	c.406C>T	p.His136Tyr	missense	Exon 3 of 4	NP_998885.1	Q8WYQ3
CHCHD10	NM_001301339.2		c.427C>T	p.His143Tyr	missense	Exon 3 of 4	NP_001288268.1	B5MBW9
CHCHD10	NR_125755.2		n.451C>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHCHD10	ENST00000484558.3	TSL:1 MANE Select	c.406C>T	p.His136Tyr	missense	Exon 3 of 4	ENSP00000418428.3	Q8WYQ3
CHCHD10	ENST00000878118.1		c.469C>T	p.His157Tyr	missense	Exon 3 of 4	ENSP00000548177.1
CHCHD10	ENST00000878120.1		c.406C>T	p.His136Tyr	missense	Exon 3 of 4	ENSP00000548179.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

249924

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461388

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111798

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.70

M_CAP

Benign

0.014

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

PhyloP100

3.2

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.044

Sift

Benign

0.12

Sift4G

Benign

0.43

Polyphen

0.035

Vest4

0.25

MVP

0.061

MPC

1.2

ClinPred

0.20

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.66

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over