chr19-44899791-CTTTTTTTTTTTTTTTTTTT-C

Variant names:

• chr19-44899791-CTTTTTTTTTTTTTTTTTTT-C
• rs10524523
• NM_001128917.2:c.644-922_644-904delTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-922_644-904delTTTTTTTTTTTTTTTTTTT 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 0.57 (11836 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 = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-922_644-904delTTTTTTTTTTTTTTTTTTT		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_644-920delTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 52761 AN: 93264 Hom.: 11838 Cov.: 0

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.581

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.566 AC: 52755 AN: 93268 Hom.: 11836 Cov.: 0 AF XY: 0.573 AC XY: 24521 AN XY: 42818

African (AFR) AF: 0.607 AC: 16632 AN: 27408

American (AMR) AF: 0.599 AC: 4287 AN: 7156

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1323 AN: 2456

East Asian (EAS) AF: 0.461 AC: 1183 AN: 2566

South Asian (SAS) AF: 0.556 AC: 1296 AN: 2332

European-Finnish (FIN) AF: 0.647 AC: 2254 AN: 3482

Middle Eastern (MID) AF: 0.588 AC: 80 AN: 136

European-Non Finnish (NFE) AF: 0.536 AC: 24561 AN: 45812

Other (OTH) AF: 0.589 AC: 741 AN: 1258

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
Mutation Taster		=100/0	polymorphism (auto)

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;