Variant 19-44891562-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001128917.2(TOMM40):c.147T>G(p.Ser49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,441,996 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 24 hom., cov: 33)

Exomes 𝑓: 0.015 ( 184 hom. )

Consequence

TOMM40
NM_001128917.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.00

Variant links:

Genes affected

TOMM40 (HGNC:18001): (translocase of outer mitochondrial membrane 40) The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

TOMM40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028074384).

BP6

Variant 19-44891562-T-G is Benign according to our data. Variant chr19-44891562-T-G is described in ClinVar as [Benign]. Clinvar id is 774355.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1814/152240) while in subpopulation NFE AF= 0.0178 (1209/67978). AF 95% confidence interval is 0.017. There are 24 homozygotes in gnomad4. There are 904 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1814 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40	NM_001128917.2 linkuse as main transcript	c.147T>G	p.Ser49Arg	missense_variant	1/9	ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7 linkuse as main transcript	c.147T>G	p.Ser49Arg	missense_variant	1/9	1	NM_001128917.2	P1	O96008-1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1814

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00984

AC:

696

AN:

70734

Hom.:

AF XY:

0.0102

AC XY:

422

AN XY:

41454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00372

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00264

Gnomad FIN exome

AF:

0.0266

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0151

AC:

19458

AN:

1289756

Hom.:

184

Cov.:

AF XY:

0.0148

AC XY:

9383

AN XY:

634026

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00273

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.0119

AC:

1814

AN:

152240

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

904

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0178

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.00941

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.000405

AC:

ESP6500EA

AF:

0.0119

AC:

ExAC

AF:

0.00276

AC:

182

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.9

DANN

Benign

0.54

DEOGEN2

Benign

0.079

T;T;.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.67

T;.;T;.;T

MetaRNN

Benign

0.0028

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.35

N;N;.;N;.

REVEL

Benign

0.0090

Sift

Benign

0.49

T;T;.;T;.

Sift4G

Benign

0.58

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.067

MutPred

0.26

Loss of glycosylation at S49 (P = 0.006);Loss of glycosylation at S49 (P = 0.006);Loss of glycosylation at S49 (P = 0.006);Loss of glycosylation at S49 (P = 0.006);Loss of glycosylation at S49 (P = 0.006);

MVP

0.043

MPC

0.057

ClinPred

0.00086

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

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