Genetic Variant TOMM7:n.466G>A (chr7-22812893-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000463284.2(TOMM7):n.466G>A 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 0.371 in 373,908 control chromosomes in the GnomAD database, including 28,567 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 0.40 ( 13879 hom., cov: 33)

Exomes 𝑓: 0.35 ( 14688 hom. )

Consequence

TOMM7
ENST00000463284.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76

Publications

20 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TOMM7	NM_019059.5 link	c.*277G>A	downstream_gene_variant	ENST00000358435.9	NP_061932.1	Q9P0U1Q75MR5
TOMM7	NR_168014.1 link	n.*81G>A	downstream_gene_variant
TOMM7	NR_168015.1 link	n.*81G>A	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM7	ENST00000358435.9 link	c.*277G>A		downstream_gene_variant		1	NM_019059.5	ENSP00000351214.4		Q9P0U1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61374

AN:

152018

Hom.:

13859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.636

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.364

GnomAD4 exome

AF:

0.348

AC:

77156

AN:

221772

Hom.:

14688

Cov.:

AF XY:

0.344

AC XY:

39550

AN XY:

114836

show subpopulations

African (AFR)

AF:

0.610

AC:

3826

AN:

6268

American (AMR)

AF:

0.317

AC:

2133

AN:

6720

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

2055

AN:

7764

East Asian (EAS)

AF:

0.628

AC:

10762

AN:

17146

South Asian (SAS)

AF:

0.352

AC:

4095

AN:

11634

European-Finnish (FIN)

AF:

0.385

AC:

6631

AN:

17226

Middle Eastern (MID)

AF:

0.279

AC:

293

AN:

1052

European-Non Finnish (NFE)

AF:

0.304

AC:

42536

AN:

139790

Other (OTH)

AF:

0.340

AC:

4825

AN:

14172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2308

4617

6925

9234

11542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.404

AC:

61449

AN:

152136

Hom.:

13879

Cov.:

AF XY:

0.404

AC XY:

30060

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.601

AC:

24951

AN:

41516

American (AMR)

AF:

0.310

AC:

4733

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

910

AN:

3472

East Asian (EAS)

AF:

0.635

AC:

3295

AN:

5186

South Asian (SAS)

AF:

0.365

AC:

1759

AN:

4822

European-Finnish (FIN)

AF:

0.372

AC:

3928

AN:

10564

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.303

AC:

20591

AN:

67976

Other (OTH)

AF:

0.364

AC:

769

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1778

3556

5334

7112

8890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.303

Hom.:

3733

Bravo

AF:

0.409

Asia WGS

AF:

0.488

AC:

1697

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.56

(source)

DANN

Benign

0.63

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over