Genetic Variant TOMM40:c.644-910_644-904dupTTTTTTT (chr19-44899791-C-CTTTTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001128917.2(TOMM40):c.644-910_644-904dupTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 11 hom., cov: 0)

Consequence

TOMM40
NM_001128917.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

124 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2 link	c.644-910_644-904dupTTTTTTT		intron_variant	Intron 5 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.644-939_644-938insTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1		O96008-1

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

143

AN:

90904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00309

Gnomad AMR

AF:

0.00192

Gnomad ASJ

AF:

0.00125

Gnomad EAS

AF:

0.000418

Gnomad SAS

AF:

0.000920

Gnomad FIN

AF:

0.000906

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00157

AC:

143

AN:

90912

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

AN XY:

41696

show subpopulations

African (AFR)

AF:

0.000483

AC:

AN:

26932

American (AMR)

AF:

0.00192

AC:

AN:

6782

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

2398

East Asian (EAS)

AF:

0.000419

AC:

AN:

2388

South Asian (SAS)

AF:

0.000923

AC:

AN:

2166

European-Finnish (FIN)

AF:

0.000906

AC:

AN:

3310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.00229

AC:

103

AN:

44928

Other (OTH)

AF:

0.00243

AC:

AN:

1234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.0

Splicing

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

Publications

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19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over