Genetic Variant TOMM40:c.436-138T>C (chr19-44893642-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.436-138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 652,948 control chromosomes in the GnomAD database, including 87,339 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 0.58 ( 27574 hom., cov: 32)

Exomes 𝑓: 0.48 ( 59765 hom. )

Consequence

TOMM40
NM_001128917.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

15 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TOMM40	NM_001128917.2	MANE Select	c.436-138T>C	intron	N/A	NP_001122389.1	O96008-1
TOMM40	NM_001128916.2		c.436-138T>C	intron	N/A	NP_001122388.1	O96008-1
TOMM40	NM_006114.3		c.436-138T>C	intron	N/A	NP_006105.1	O96008-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.436-138T>C	intron	N/A	ENSP00000410339.1	O96008-1
TOMM40	ENST00000252487.9	TSL:1	c.436-138T>C	intron	N/A	ENSP00000252487.4	O96008-1
TOMM40	ENST00000405636.6	TSL:1	c.436-138T>C	intron	N/A	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88407

AN:

151966

Hom.:

27534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.481

Gnomad OTH

AF:

0.575

GnomAD4 exome

AF:

0.480

AC:

240297

AN:

500864

Hom.:

59765

AF XY:

0.476

AC XY:

123908

AN XY:

260212

show subpopulations

African (AFR)

AF:

0.825

AC:

9899

AN:

12002

American (AMR)

AF:

0.584

AC:

10054

AN:

17230

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

6939

AN:

13432

East Asian (EAS)

AF:

0.311

AC:

8662

AN:

27896

South Asian (SAS)

AF:

0.423

AC:

18722

AN:

44300

European-Finnish (FIN)

AF:

0.524

AC:

18706

AN:

35692

Middle Eastern (MID)

AF:

0.495

AC:

993

AN:

2008

European-Non Finnish (NFE)

AF:

0.476

AC:

152760

AN:

321166

Other (OTH)

AF:

0.500

AC:

13562

AN:

27138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5864

11729

17593

23458

29322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1854

3708

5562

7416

9270

<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:

0.582

AC:

88508

AN:

152084

Hom.:

27574

Cov.:

AF XY:

0.581

AC XY:

43222

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.821

AC:

34066

AN:

41508

American (AMR)

AF:

0.570

AC:

8709

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1764

AN:

3472

East Asian (EAS)

AF:

0.324

AC:

1672

AN:

5164

South Asian (SAS)

AF:

0.432

AC:

2085

AN:

4828

European-Finnish (FIN)

AF:

0.536

AC:

5670

AN:

10586

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.481

AC:

32684

AN:

67942

Other (OTH)

AF:

0.573

AC:

1208

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1793

3587

5380

7174

8967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.581

Hom.:

6114

Bravo

AF:

0.596

Asia WGS

AF:

0.423

AC:

1474

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.7

(source)

DANN

Benign

0.43

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over