19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CT

Variant names:

• chr19-44899791-CTTTTTTTTTTTTTTTTTTTTTT-C
• rs10524523
• NM_001128917.2:c.644-925_644-904delTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001128917.2(TOMM40):​c.644-925_644-904delTTTTTTTTTTTTTTTTTTTTTT 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 0.0013 (6 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.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00129 (117/91002) while in subpopulation EAS AF = 0.0391 (94/2404). AF 95% confidence interval is 0.0327. There are 6 homozygotes in GnomAd4. There are 73 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-925_644-904delTTTTTTTTTTTTTTTTTTTTTT		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_644-917delTTTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 118 AN: 90996 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.0000371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.00687

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000890

Gnomad OTH AF: 0.00163

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

GnomAD4 genome AF: 0.00129 AC: 117 AN: 91002 Hom.: 6 Cov.: 0 AF XY: 0.00175 AC XY: 73 AN XY: 41744

African (AFR) AF: 0.0000371 AC: 1 AN: 26944

American (AMR) AF: 0.000147 AC: 1 AN: 6800

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

East Asian (EAS) AF: 0.0391 AC: 94 AN: 2404

South Asian (SAS) AF: 0.00690 AC: 15 AN: 2174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3310

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

European-Non Finnish (NFE) AF: 0.0000890 AC: 4 AN: 44956

Other (OTH) AF: 0.00162 AC: 2 AN: 1238

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;