Genetic Variant TOMM7:n.298A>G (chr7-22817885-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 ENST00000496129.1(TOMM7):n.298A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 989,414 control chromosomes in the GnomAD database, including 93,122 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 0.48 ( 19431 hom., cov: 32)

Exomes 𝑓: 0.40 ( 73691 hom. )

Consequence

TOMM7
ENST00000496129.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

21 publications found

Variant links:

Genes affected

TOMM7 (HGNC:21648): (translocase of outer mitochondrial membrane 7) This gene encodes a subunit of the translocase of the outer mitochondrial membrane. The encoded protein regulates the assembly and stability of the translocase complex. [provided by RefSeq, Oct 2012]

TOMM7 Gene-Disease associations (from GenCC):

Garg-Mishra progeroid syndrome
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics

TOMM7 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 (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TOMM7	NM_019059.5 link	c.152+115A>G	intron_variant	Intron 2 of 2	ENST00000358435.9	NP_061932.1	Q9P0U1Q75MR5
TOMM7	NR_168014.1 link	n.178+115A>G	intron_variant	Intron 2 of 2
TOMM7	NR_168015.1 link	n.130-4700A>G	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM7	ENST00000358435.9 link	c.152+115A>G		intron_variant	Intron 2 of 2	1	NM_019059.5	ENSP00000351214.4		Q9P0U1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73045

AN:

151868

Hom.:

19402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.686

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.401

AC:

335908

AN:

837424

Hom.:

73691

Cov.:

AF XY:

0.403

AC XY:

174144

AN XY:

432538

show subpopulations

African (AFR)

AF:

0.691

AC:

14176

AN:

20518

American (AMR)

AF:

0.493

AC:

16674

AN:

33820

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

5957

AN:

19598

East Asian (EAS)

AF:

0.823

AC:

28674

AN:

34844

South Asian (SAS)

AF:

0.512

AC:

32401

AN:

63288

European-Finnish (FIN)

AF:

0.419

AC:

20675

AN:

49402

Middle Eastern (MID)

AF:

0.340

AC:

1222

AN:

3590

European-Non Finnish (NFE)

AF:

0.349

AC:

200189

AN:

573562

Other (OTH)

AF:

0.411

AC:

15940

AN:

38802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8817

17634

26450

35267

44084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4876

9752

14628

19504

24380

<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:

0.481

AC:

73135

AN:

151990

Hom.:

19431

Cov.:

AF XY:

0.484

AC XY:

36004

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.686

AC:

28428

AN:

41448

American (AMR)

AF:

0.452

AC:

6914

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1055

AN:

3468

East Asian (EAS)

AF:

0.819

AC:

4240

AN:

5176

South Asian (SAS)

AF:

0.535

AC:

2577

AN:

4818

European-Finnish (FIN)

AF:

0.409

AC:

4315

AN:

10540

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24132

AN:

67932

Other (OTH)

AF:

0.432

AC:

912

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1783

3566

5350

7133

8916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.399

Hom.:

8785

Bravo

AF:

0.497

Asia WGS

AF:

0.649

AC:

2257

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.089

(source)

DANN

Benign

0.70

PhyloP100

-1.5

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

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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