dbSNP rs951686050: CHCHD10:p.Arg11Trp (chr22-23767844-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_213720.3(CHCHD10):c.31C>T(p.Arg11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 1,521,686 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CHCHD10
NM_213720.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.436

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37536743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD10	NM_213720.3 link	c.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 4	ENST00000484558.3	NP_998885.1	Q8WYQ3
CHCHD10	NM_001301339.2 link	c.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 4		NP_001288268.1	Q8WYQ3B5MBW9
CHCHD10	NR_125755.2 link	n.129C>T		non_coding_transcript_exon_variant	Exon 1 of 4
CHCHD10	NR_125756.2 link	n.129C>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.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 4	1	NM_213720.3	ENSP00000418428.3	Q8WYQ3
CHCHD10	ENST00000401675.7 link	c.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 4	5		ENSP00000384973.3	B5MBW9
CHCHD10	ENST00000520222.1 link	c.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 3	3		ENSP00000430042.1	E5RH03
CHCHD10	ENST00000517886.1 link	n.31C>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000429976.1	E5RGN4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152134

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000219

AC:

AN:

1369552

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000361

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 10, 2023

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BP4, PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.12

.;T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.64

T;T;T

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.3

.;.;M

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-8.0

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0060

.;D;D

Sift4G

Uncertain

0.014

.;D;D

Polyphen

1.0

.;.;D

Vest4

0.31

MutPred

0.35

Loss of methylation at R11 (P = 0.0143);Loss of methylation at R11 (P = 0.0143);Loss of methylation at R11 (P = 0.0143);

MVP

0.35

MPC

0.52

ClinPred

0.99

GERP RS

2.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.2

Varity_R

0.12

gMVP

0.42

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

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