19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTT

Variant names:

• chr19-44899791-CTTTTTTTTTTTTTTTTTT-C
• rs10524523
• NM_001128917.2:c.644-921_644-904delTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001128917.2(TOMM40):​c.644-921_644-904delTTTTTTTTTTTTTTTTTT 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 0.0010 (0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-921_644-904delTTTTTTTTTTTTTTTTTT		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_644-921delTTTTTTTTTTTTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 92 AN: 90948 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.00138

Gnomad FIN AF: 0.000302

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.000645

Gnomad OTH AF: 0.00326

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

GnomAD4 genome AF: 0.00101 AC: 92 AN: 90956 Hom.: 0 Cov.: 0 AF XY: 0.00101 AC XY: 42 AN XY: 41716

African (AFR) AF: 0.00115 AC: 31 AN: 26930

American (AMR) AF: 0.00118 AC: 8 AN: 6794

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

East Asian (EAS) AF: 0.00584 AC: 14 AN: 2396

South Asian (SAS) AF: 0.00138 AC: 3 AN: 2170

European-Finnish (FIN) AF: 0.000302 AC: 1 AN: 3314

Middle Eastern (MID) AF: 0.0156 AC: 2 AN: 128

European-Non Finnish (NFE) AF: 0.000645 AC: 29 AN: 44940

Other (OTH) AF: 0.00323 AC: 4 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;