Genetic Variant NM_001128917.2:c.644-906_644-904dupTTT (chr19-44899791-C-CTTT) – 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.644-906_644-904dupTTT 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 0.0046 ( 31 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 419 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2 link	c.644-906_644-904dupTTT		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_644-938insTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1		O96008-1

Frequencies

GnomAD3 genomes

AF:

0.00461

AC:

419

AN:

90900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00154

Gnomad AMR

AF:

0.00325

Gnomad ASJ

AF:

0.00961

Gnomad EAS

AF:

0.00167

Gnomad SAS

AF:

0.00322

Gnomad FIN

AF:

0.000303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00696

Gnomad OTH

AF:

0.00327

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

GnomAD4 genome

AF:

0.00461

AC:

419

AN:

90908

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

195

AN XY:

41686

show subpopulations

African (AFR)

AF:

0.00163

AC:

AN:

26926

American (AMR)

AF:

0.00324

AC:

AN:

6782

Ashkenazi Jewish (ASJ)

AF:

0.00961

AC:

AN:

2394

East Asian (EAS)

AF:

0.00167

AC:

AN:

2392

South Asian (SAS)

AF:

0.00323

AC:

AN:

2166

European-Finnish (FIN)

AF:

0.000303

AC:

AN:

3304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

126

European-Non Finnish (NFE)

AF:

0.00697

AC:

313

AN:

44934

Other (OTH)

AF:

0.00324

AC:

AN:

1234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

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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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