Genetic Variant C22orf15:c.*15C>T (chr22-23765747-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001331041.2(C22orf15):c.467C>T(p.Thr156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,550,786 control chromosomes in the GnomAD database, including 1,572 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 835 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 737 hom. )

Consequence

C22orf15
NM_001331041.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0410

Variant links:

Genes affected

C22orf15 (HGNC:15558): (chromosome 22 open reading frame 15)

C22orf15 links:

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=0.0020511746).

BP6

Variant 22-23765747-C-T is Benign according to our data. Variant chr22-23765747-C-T is described in ClinVar as [Benign]. Clinvar id is 1238466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C22orf15	NM_182520.3 link	c.*15C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000402217.8	NP_872326.2	Q8WYQ4-1
CHCHD10	NM_213720.3 link	c.*260G>A		downstream_gene_variant		ENST00000484558.3	NP_998885.1	Q8WYQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C22orf15	ENST00000402217.8 link	c.*15C>T		3_prime_UTR_variant	Exon 6 of 6	2	NM_182520.3	ENSP00000384965.4		Q8WYQ4-1
CHCHD10	ENST00000484558.3 link	c.*260G>A		downstream_gene_variant		1	NM_213720.3	ENSP00000418428.3		Q8WYQ3

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8705

AN:

152148

Hom.:

833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.0416

GnomAD3 exomes

AF:

0.0126

AC:

1967

AN:

155640

Hom.:

157

AF XY:

0.00981

AC XY:

809

AN XY:

82464

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000221

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000815

Gnomad OTH exome

AF:

0.00527

GnomAD4 exome

AF:

0.00588

AC:

8225

AN:

1398520

Hom.:

737

Cov.:

AF XY:

0.00507

AC XY:

3494

AN XY:

689678

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.0000796

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000266

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0573

AC:

8719

AN:

152266

Hom.:

835

Cov.:

AF XY:

0.0547

AC XY:

4072

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0259

Hom.:

204

Bravo

AF:

0.0651

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0137

AC:

554

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.1

DANN

Benign

0.87

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.33

REVEL

Benign

0.010

Sift

Pathogenic

0.0

Vest4

0.057

ClinPred

0.0018

GERP RS

-0.16

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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