19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr19-44899791-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTT
• rs10524523
• NM_001128917.2:c.644-930_644-904dupTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001128917.2(TOMM40):​c.644-930_644-904dupTTTTTTTTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000011 (0 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 124 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	NM_001128917.2	MANE Select	c.644-930_644-904dupTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.644-930_644-904dupTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.644-930_644-904dupTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_006105.1	O96008-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.644-939_644-938insTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000410339.1	O96008-1
	TOMM40	ENST00000252487.9	TSL:1	c.644-939_644-938insTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000252487.4	O96008-1
	TOMM40	ENST00000405636.6	TSL:1	c.644-939_644-938insTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes AF: 0.0000110 AC: 1 AN: 90984 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000110 AC: 1 AN: 90984 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 41714

African (AFR) AF: 0.0000371 AC: 1 AN: 26920

American (AMR) AF: 0.00 AC: 0 AN: 6794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2398

East Asian (EAS) AF: 0.00 AC: 0 AN: 2398

South Asian (SAS) AF: 0.00 AC: 0 AN: 2182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44964

Other (OTH) AF: 0.00 AC: 0 AN: 1228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs10524523; hg19: chr19-45403048;