NM_001128917.2:c.644-924_644-904delTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr19-44899791-CTTTTTTTTTTTTTTTTTTTTT-C
• rs10524523
• NM_001128917.2:c.644-924_644-904delTTTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-924_644-904delTTTTTTTTTTTTTTTTTTTTT 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 0.00022 (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 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-924_644-904delTTTTTTTTTTTTTTTTTTTTT		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_644-918delTTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.000220 AC: 20 AN: 90976 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000417

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000156

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000220 AC: 20 AN: 90984 Hom.: 0 Cov.: 0 AF XY: 0.000288 AC XY: 12 AN XY: 41728

African (AFR) AF: 0.000223 AC: 6 AN: 26940

American (AMR) AF: 0.000294 AC: 2 AN: 6798

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

East Asian (EAS) AF: 0.000418 AC: 1 AN: 2394

South Asian (SAS) AF: 0.00 AC: 0 AN: 2174

European-Finnish (FIN) AF: 0.00121 AC: 4 AN: 3310

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

European-Non Finnish (NFE) AF: 0.000156 AC: 7 AN: 44954

Other (OTH) AF: 0.00 AC: 0 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;