rs374353973

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213720.3(CHCHD10):c.274G>T(p.Ala92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 711,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A92T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHCHD10
NM_213720.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.886

Publications

0 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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
frontotemporal dementia and/or amyotrophic lateral sclerosis 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD10	NM_213720.3 link	c.274G>T	p.Ala92Ser	missense_variant	Exon 3 of 4	ENST00000484558.3	NP_998885.1	Q8WYQ3
CHCHD10	NM_001301339.2 link	c.295G>T	p.Ala99Ser	missense_variant	Exon 3 of 4		NP_001288268.1	Q8WYQ3B5MBW9
CHCHD10	NR_125755.2 link	n.319G>T		non_coding_transcript_exon_variant	Exon 3 of 4
CHCHD10	NR_125756.2 link	n.152G>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD10	ENST00000484558.3 link	c.274G>T	p.Ala92Ser	missense_variant	Exon 3 of 4	1	NM_213720.3	ENSP00000418428.3		Q8WYQ3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

79792

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000281

AC:

AN:

711244

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

356032

show subpopulations

African (AFR)

AF:

0.0000544

AC:

AN:

18382

American (AMR)

AF:

0.00

AC:

AN:

21330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14952

East Asian (EAS)

AF:

0.00

AC:

AN:

21834

South Asian (SAS)

AF:

0.00

AC:

AN:

43822

European-Finnish (FIN)

AF:

0.0000345

AC:

AN:

28986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2166

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

529300

Other (OTH)

AF:

0.00

AC:

AN:

30472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

79792

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

38338

African (AFR)

AF:

0.00

AC:

AN:

24162

American (AMR)

AF:

0.00

AC:

AN:

7166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1944

East Asian (EAS)

AF:

0.00

AC:

AN:

2850

South Asian (SAS)

AF:

0.00

AC:

AN:

2134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

36088

Other (OTH)

AF:

0.00

AC:

AN:

1032

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.36

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.0091

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.27

T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L

PhyloP100

-0.89

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.012

Sift

Benign

0.77

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.037

.;B

Vest4

0.13

MutPred

0.23

.;Gain of glycosylation at A92 (P = 0.0221);

MVP

0.030

MPC

0.77

ClinPred

0.030

GERP RS

-6.6

Varity_R

0.063

gMVP

0.37

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -12

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over