rs200831077

Positions:

chr22-23767499-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_213720.3(CHCHD10):c.136G>T(p.Ala46Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000691 in 1,556,750 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 5 hom. )

Consequence

CHCHD10
NM_213720.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008496523).

BP6

Variant 22-23767499-C-A is Benign according to our data. Variant chr22-23767499-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 473420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00387 (589/152282) while in subpopulation AFR AF= 0.0132 (549/41566). AF 95% confidence interval is 0.0123. There are 7 homozygotes in gnomad4. There are 264 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 589 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHCHD10	NM_213720.3 linkuse as main transcript	c.136G>T	p.Ala46Ser	missense_variant	2/4	ENST00000484558.3	NP_998885.1
CHCHD10	NM_001301339.2 linkuse as main transcript	c.136G>T	p.Ala46Ser	missense_variant	2/4		NP_001288268.1
CHCHD10	NR_125755.2 linkuse as main transcript	n.181G>T		non_coding_transcript_exon_variant	2/4
CHCHD10	NR_125756.2 linkuse as main transcript	n.139+335G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CHCHD10	ENST00000484558.3 linkuse as main transcript	c.136G>T	p.Ala46Ser	missense_variant	2/4	1	NM_213720.3	ENSP00000418428	P1
CHCHD10	ENST00000401675.7 linkuse as main transcript	c.136G>T	p.Ala46Ser	missense_variant	2/4	5		ENSP00000384973
CHCHD10	ENST00000520222.1 linkuse as main transcript	c.41+335G>T		intron_variant		3		ENSP00000430042
CHCHD10	ENST00000517886.1 linkuse as main transcript	c.83G>T	p.Gly28Val	missense_variant, NMD_transcript_variant	2/4	3		ENSP00000429976

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

585

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000686

AC:

109

AN:

158892

Hom.:

AF XY:

0.000482

AC XY:

AN XY:

89140

show subpopulations

Gnomad AFR exome

AF:

0.0145

Gnomad AMR exome

AF:

0.000652

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000416

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000154

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000347

AC:

487

AN:

1404468

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

191

AN XY:

695174

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.000982

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000617

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.00387

AC:

589

AN:

152282

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

264

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000886

Hom.:

Bravo

AF:

0.00430

ESP6500AA

AF:

0.00949

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000792

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2020	- -

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 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.15

Sift

Benign

0.048

D;T

Sift4G

Benign

0.061

T;T

Polyphen

1.0

.;D

Vest4

0.54

MVP

0.16

MPC

0.97

ClinPred

0.044

GERP RS

2.6

Varity_R

0.15

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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