dbSNP rs741780: TOMM40:c.844-34T>C (chr19-44901174-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128917.2(TOMM40):c.844-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,613,054 control chromosomes in the GnomAD database, including 166,521 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20578 hom., cov: 33)

Exomes 𝑓: 0.44 ( 145943 hom. )

Consequence

TOMM40
NM_001128917.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.84

Publications

28 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2 link	c.844-34T>C		intron_variant	Intron 7 of 8	ENST00000426677.7	NP_001122389.1	O96008-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7 link	c.844-34T>C		intron_variant	Intron 7 of 8	1	NM_001128917.2	ENSP00000410339.1		O96008-1

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77823

AN:

152052

Hom.:

20561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.530

GnomAD2 exomes

AF:

0.470

AC:

117121

AN:

249232

AF XY:

0.461

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.585

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.447

Gnomad OTH exome

AF:

0.462

GnomAD4 exome

AF:

0.443

AC:

647254

AN:

1460886

Hom.:

145943

Cov.:

AF XY:

0.441

AC XY:

320507

AN XY:

726730

show subpopulations

African (AFR)

AF:

0.642

AC:

21504

AN:

33474

American (AMR)

AF:

0.576

AC:

25699

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12436

AN:

26124

East Asian (EAS)

AF:

0.306

AC:

12136

AN:

39684

South Asian (SAS)

AF:

0.399

AC:

34436

AN:

86230

European-Finnish (FIN)

AF:

0.500

AC:

26693

AN:

53350

Middle Eastern (MID)

AF:

0.450

AC:

2587

AN:

5748

European-Non Finnish (NFE)

AF:

0.437

AC:

485184

AN:

1111308

Other (OTH)

AF:

0.440

AC:

26579

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

21786

43572

65359

87145

108931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14756

29512

44268

59024

73780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.512

AC:

77890

AN:

152168

Hom.:

20578

Cov.:

AF XY:

0.512

AC XY:

38085

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.644

AC:

26757

AN:

41522

American (AMR)

AF:

0.535

AC:

8178

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1627

AN:

3472

East Asian (EAS)

AF:

0.314

AC:

1624

AN:

5178

South Asian (SAS)

AF:

0.402

AC:

1939

AN:

4826

European-Finnish (FIN)

AF:

0.510

AC:

5393

AN:

10584

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30621

AN:

67984

Other (OTH)

AF:

0.528

AC:

1116

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1984

3968

5953

7937

9921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.499

Hom.:

4094

Bravo

AF:

0.521

Asia WGS

AF:

0.389

AC:

1355

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

(source)

DANN

Benign

0.71

PhyloP100

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over