Genetic Variant NM_001128917.2:c.644-908_644-904dupTTTTT (chr19-44899791-C-CTTTTT) – 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.644-908_644-904dupTTTTT 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 0.0019 ( 14 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 170 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2 link	c.644-908_644-904dupTTTTT		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_644-938insTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1		O96008-1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

170

AN:

90866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000632

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.00207

Gnomad ASJ

AF:

0.00417

Gnomad EAS

AF:

0.00210

Gnomad SAS

AF:

0.000460

Gnomad FIN

AF:

0.000606

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00164

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

GnomAD4 genome

AF:

0.00187

AC:

170

AN:

90874

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

AN XY:

41684

show subpopulations

African (AFR)

AF:

0.000632

AC:

AN:

26920

American (AMR)

AF:

0.00206

AC:

AN:

6780

Ashkenazi Jewish (ASJ)

AF:

0.00417

AC:

AN:

2400

East Asian (EAS)

AF:

0.00210

AC:

AN:

2376

South Asian (SAS)

AF:

0.000463

AC:

AN:

2162

European-Finnish (FIN)

AF:

0.000606

AC:

AN:

3302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

128

European-Non Finnish (NFE)

AF:

0.00254

AC:

114

AN:

44926

Other (OTH)

AF:

0.00163

AC:

AN:

1230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over