NM_001128917.2:c.643+1393A>C

Variant names:

• chr19-44895459-A-C
• rs157590
• NM_001128917.2:c.643+1393A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128917.2(TOMM40):​c.643+1393A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,798 control chromosomes in the GnomAD database, including 28,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28236 hom., cov: 30)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.643+1393A>C		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.643+1393A>C		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89261 AN: 151680 Hom.: 28191 Cov.: 30

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.589 AC: 89369 AN: 151798 Hom.: 28236 Cov.: 30 AF XY: 0.588 AC XY: 43614 AN XY: 74146

African (AFR) AF: 0.838 AC: 34682 AN: 41406

American (AMR) AF: 0.579 AC: 8827 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1765 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1696 AN: 5150

South Asian (SAS) AF: 0.433 AC: 2078 AN: 4804

European-Finnish (FIN) AF: 0.536 AC: 5630 AN: 10506

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32802 AN: 67896

Other (OTH) AF: 0.586 AC: 1239 AN: 2114

Alfa AF: 0.551 Hom.: 9936

Bravo AF: 0.605

Asia WGS AF: 0.436 AC: 1519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.69
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs157590; hg19: chr19-45398716;