22-23767854-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_213720.3(CHCHD10):c.21C>T(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CHCHD10
NM_213720.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.124

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: Benign. The variant received -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 22-23767854-G-A is Benign according to our data. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-23767854-G-A is described in CliVar as Likely_benign. Clinvar id is 473422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.124 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD10	NM_213720.3 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 1 of 4	ENST00000484558.3	NP_998885.1	Q8WYQ3
CHCHD10	NM_001301339.2 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 1 of 4		NP_001288268.1	Q8WYQ3B5MBW9
CHCHD10	NR_125755.2 link	n.119C>T		non_coding_transcript_exon_variant	Exon 1 of 4
CHCHD10	NR_125756.2 link	n.119C>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHCHD10	ENST00000484558.3 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 1 of 4	1	NM_213720.3	ENSP00000418428.3	Q8WYQ3
CHCHD10	ENST00000401675.7 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 1 of 4	5		ENSP00000384973.3	B5MBW9
CHCHD10	ENST00000520222.1 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 1 of 3	3		ENSP00000430042.1	E5RH03
CHCHD10	ENST00000517886.1 link	n.21C>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000429976.1	E5RGN4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1366490

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27710

American (AMR)

AF:

0.0000318

AC:

AN:

31428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22978

East Asian (EAS)

AF:

0.00

AC:

AN:

32088

South Asian (SAS)

AF:

0.00

AC:

AN:

76290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065268

Other (OTH)

AF:

0.00

AC:

AN:

55770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Jul 11, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

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

Feb 11, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.3

(source)

DANN

Benign

0.96

PhyloP100

-0.12

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over