Variant 17-997239-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013337.4(TIMM22):c.97G>C(p.Val33Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00624 in 1,613,452 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 32 hom. )

Consequence

TIMM22
NM_013337.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 4.42

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=0.008468449).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM22	NM_013337.4 linkuse as main transcript	c.97G>C	p.Val33Leu	missense_variant	1/4	ENST00000327158.5	NP_037469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM22	ENST00000327158.5 linkuse as main transcript	c.97G>C	p.Val33Leu	missense_variant	1/4	1	NM_013337.4	ENSP00000320236	P1

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

661

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000752

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00705

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00423

AC:

1057

AN:

249592

Hom.:

AF XY:

0.00416

AC XY:

564

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00790

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.000696

Gnomad NFE exome

AF:

0.00672

Gnomad OTH exome

AF:

0.00706

GnomAD4 exome

AF:

0.00644

AC:

9405

AN:

1461088

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

4520

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.00830

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.000910

Gnomad4 NFE exome

AF:

0.00758

Gnomad4 OTH exome

AF:

0.00689

GnomAD4 genome

AF:

0.00433

AC:

660

AN:

152364

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000752

Gnomad4 NFE

AF:

0.00706

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00458

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00402

AC:

487

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00699

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation deficiency 43

Pathogenic:1Uncertain:1

Uncertain significance, criteria provided, single submitter	clinical testing	Mendelics	Oct 21, 2022	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 24, 2020	- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

TIMM22: PM3, PS3:Moderate, PM2:Supporting, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.048

MetaRNN

Benign

0.0085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

REVEL

Benign

0.098

Sift

Benign

0.032

Sift4G

Benign

0.13

Polyphen

0.36

Vest4

0.39

MutPred

0.27

Loss of helix (P = 0.0558);

MVP

0.34

MPC

0.18

ClinPred

0.057

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.66

gMVP

0.71

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