rs741780

Positions:

• chr19-44901174-T-C
• chr19-44901174-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128917.2(TOMM40):​c.844-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,613,054 control chromosomes in the GnomAD database, including 166,521 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 0.51 (20578 hom., cov: 33)
  • Exomes 𝑓: 0.44 (145943 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.84

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.844-34T>C		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.844-34T>C		intron_variant		1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77823 AN: 152052 Hom.: 20561 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.530

GnomAD3 exomes AF: 0.470 AC: 117121 AN: 249232 Hom.: 28365 AF XY: 0.461 AC XY: 62116 AN XY: 134774

Gnomad AFR exome AF: 0.645

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.401

Gnomad FIN exome AF: 0.498

Gnomad NFE exome AF: 0.447

Gnomad OTH exome AF: 0.462

GnomAD4 exome AF: 0.443 AC: 647254 AN: 1460886 Hom.: 145943 Cov.: 37 AF XY: 0.441 AC XY: 320507 AN XY: 726730

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.512 AC: 77890 AN: 152168 Hom.: 20578 Cov.: 33 AF XY: 0.512 AC XY: 38085 AN XY: 74382

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.528

Alfa AF: 0.499 Hom.: 4094

Bravo AF: 0.521

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs741780; hg19: chr19-45404431; COSMIC: COSV52984969; COSMIC: COSV52984969;