rs157584

chr19-44893642-T-Cchr19-44893642-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.436-138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 652,948 control chromosomes in the GnomAD database, including 87,339 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 0.58 (27574 hom., cov: 32)
  • Exomes 𝑓: 0.48 (59765 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40	NM_001128917.2	c.436-138T>C		intron_variant		ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7	c.436-138T>C		intron_variant		1	NM_001128917.2	P1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88407 AN: 151966 Hom.: 27534 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.575

GnomAD4 exome AF: 0.480 AC: 240297 AN: 500864 Hom.: 59765 AF XY: 0.476 AC XY: 123908 AN XY: 260212

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.582 AC: 88508 AN: 152084 Hom.: 27574 Cov.: 32 AF XY: 0.581 AC XY: 43222 AN XY: 74354

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.573

Alfa AF: 0.569 Hom.: 5115

Bravo AF: 0.596

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.7
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs157584; hg19: chr19-45396899; COSMIC: COSV52977017; COSMIC: COSV52977017;