Variant 17-998823-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_013337.4(TIMM22):c.283G>A(p.Asp95Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,614,036 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00087 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 14 hom. )

Consequence

TIMM22
NM_013337.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.49

Variant links:

Genes affected

TIMM22 (HGNC:17317): (translocase of inner mitochondrial membrane 22) Multipass transmembrane proteins are brought into mitochondria and inserted into the mitochondrial inner membrane by way of the TIM22 complex. This complex has six subunits and is a twin-pore translocase. The protein encoded by this gene is a subunit of TIM22 and represents the voltage-activated and signal-gated channel. [provided by RefSeq, Jul 2016]

TIMM22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.177582).

BP6

Variant 17-998823-G-A is Benign according to our data. Variant chr17-998823-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647180.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM22	NM_013337.4 link	c.283G>A	p.Asp95Asn	missense_variant	Exon 2 of 4	ENST00000327158.5	NP_037469.2	Q9Y584

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM22	ENST00000327158.5 link	c.283G>A	p.Asp95Asn	missense_variant	Exon 2 of 4	1	NM_013337.4	ENSP00000320236.2		Q9Y584

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00106

AC:

266

AN:

251314

Hom.:

AF XY:

0.00130

AC XY:

177

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00165

AC:

2405

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1232

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000874

AC:

133

AN:

152252

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.000865

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00105

AC:

127

EpiCase

AF:

0.00185

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TIMM22: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.052

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.65

REVEL

Benign

0.18

Sift

Benign

0.51

Sift4G

Benign

0.63

Polyphen

1.0

Vest4

0.84

MVP

0.33

MPC

0.63

ClinPred

0.074

GERP RS

5.4

Varity_R

0.16

gMVP

0.91

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