Variant 3-100375052-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014820.5(TOMM70):c.1193C>T(p.Pro398Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,608,148 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 0.00076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

TOMM70
NM_014820.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

Variant links:

Genes affected

TOMM70 (HGNC:11985): (translocase of outer mitochondrial membrane 70) This gene encodes an import receptor of the outer mitochondrial membrane that is part of the translocase of the outer membrane complex. This protein is involved in the import of mitochondrial precursor proteins. The protein interacts with the SARS-CoV and SARS-Cov-2 ORF9b proteins. [provided by RefSeq, Dec 2021]

TOMM70 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17345425).

BS2

High AC in GnomAd4 at 116 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM70	NM_014820.5 link	c.1193C>T	p.Pro398Leu	missense_variant	7/12	ENST00000284320.6	NP_055635.3	O94826

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM70	ENST00000284320.6 link	c.1193C>T	p.Pro398Leu	missense_variant	7/12	1	NM_014820.5	ENSP00000284320.5		O94826

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000783

AC:

192

AN:

245310

Hom.:

AF XY:

0.000769

AC XY:

102

AN XY:

132670

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.00140

AC:

2042

AN:

1455880

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

984

AN XY:

724114

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.000665

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000577

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00120

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152268

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.000714

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.1193C>T (p.P398L) alteration is located in exon 7 (coding exon 7) of the TOMM70 gene. This alteration results from a C to T substitution at nucleotide position 1193, causing the proline (P) at amino acid position 398 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.17

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

4.0

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.50

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.024

Polyphen

0.94

Vest4

0.58

MVP

0.22

MPC

1.4

ClinPred

0.23

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.65

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