19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTT

Variant names:

• chr19-44899791-CTTTTTTTTTTTTTTTTTTTT-C
• rs10524523
• NM_001128917.2:c.644-923_644-904delTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001128917.2(TOMM40):​c.644-923_644-904delTTTTTTTTTTTTTTTTTTTT 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 DEL_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 0.031 (135 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-923_644-904delTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 5 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-938_644-919delTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 2849 AN: 91048 Hom.: 135 Cov.: 0

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.000417

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00756

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000957

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0313 AC: 2852 AN: 91058 Hom.: 135 Cov.: 0 AF XY: 0.0325 AC XY: 1359 AN XY: 41782

African (AFR) AF: 0.0966 AC: 2609 AN: 27012

American (AMR) AF: 0.0165 AC: 112 AN: 6804

Ashkenazi Jewish (ASJ) AF: 0.000417 AC: 1 AN: 2398

East Asian (EAS) AF: 0.0167 AC: 40 AN: 2400

South Asian (SAS) AF: 0.00230 AC: 5 AN: 2174

European-Finnish (FIN) AF: 0.00756 AC: 25 AN: 3308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 128

European-Non Finnish (NFE) AF: 0.000957 AC: 43 AN: 44944

Other (OTH) AF: 0.0137 AC: 17 AN: 1240

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50

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;