NM_001128917.2:c.644-915_644-904dupTTTTTTTTTTTT

Variant names:

• chr19-44899791-C-CTTTTTTTTTTTT
• rs10524523
• NM_001128917.2:c.644-915_644-904dupTTTTTTTTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-915_644-904dupTTTTTTTTTTTT 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 0.00012 (2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-915_644-904dupTTTTTTTTTTTT		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.644-939_644-938insTTTTTTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.000121 AC: 11 AN: 90984 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0000371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000294

Gnomad ASJ AF: 0.00125

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000458

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000890

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000121 AC: 11 AN: 90992 Hom.: 2 Cov.: 0 AF XY: 0.000168 AC XY: 7 AN XY: 41732

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

American (AMR) AF: 0.000294 AC: 2 AN: 6796

Ashkenazi Jewish (ASJ) AF: 0.00125 AC: 3 AN: 2398

East Asian (EAS) AF: 0.00 AC: 0 AN: 2394

South Asian (SAS) AF: 0.000460 AC: 1 AN: 2174

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

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

European-Non Finnish (NFE) AF: 0.0000890 AC: 4 AN: 44958

Other (OTH) AF: 0.00 AC: 0 AN: 1238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;