Variant 17-999629-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013337.4(TIMM22):c.508+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,587,166 control chromosomes in the GnomAD database, including 70,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4831 hom., cov: 29)

Exomes 𝑓: 0.29 ( 66064 hom. )

Consequence

TIMM22
NM_013337.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.787

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-999629-A-G is Benign according to our data. Variant chr17-999629-A-G is described in ClinVar as [Benign]. Clinvar id is 1342211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM22	NM_013337.4 linkuse as main transcript	c.508+45A>G		intron_variant		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.508+45A>G		intron_variant		1	NM_013337.4	ENSP00000320236	P1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32970

AN:

151806

Hom.:

4833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0784

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.229

AC:

56431

AN:

246294

Hom.:

8369

AF XY:

0.232

AC XY:

30865

AN XY:

133220

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.261

Gnomad EAS exome

AF:

0.00111

Gnomad SAS exome

AF:

0.0902

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.288

AC:

413926

AN:

1435242

Hom.:

66064

Cov.:

AF XY:

0.284

AC XY:

203194

AN XY:

715206

show subpopulations

Gnomad4 AFR exome

AF:

0.0466

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.000762

Gnomad4 SAS exome

AF:

0.0914

Gnomad4 FIN exome

AF:

0.350

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.217

AC:

32956

AN:

151924

Hom.:

4831

Cov.:

AF XY:

0.212

AC XY:

15707

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0560

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0785

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.281

Hom.:

2008

Bravo

AF:

0.198

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation deficiency 43

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.2

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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