rs157582

Positions:

• chr19-44892962-C-T

Variant summary

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

The NM_001128917.2(TOMM40):​c.435+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,560,052 control chromosomes in the GnomAD database, including 43,042 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 0.29 (7124 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35918 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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 = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.435+33C>T		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.435+33C>T		intron_variant		1	NM_001128917.2	ENSP00000410339	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43266 AN: 151914 Hom.: 7092 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.240 AC: 54992 AN: 229254 Hom.: 6893 AF XY: 0.230 AC XY: 28386 AN XY: 123546

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.222 AC: 312343 AN: 1408020 Hom.: 35918 Cov.: 23 AF XY: 0.219 AC XY: 153778 AN XY: 700788

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.285 AC: 43360 AN: 152032 Hom.: 7124 Cov.: 32 AF XY: 0.286 AC XY: 21282 AN XY: 74314

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.245

Alfa AF: 0.216 Hom.: 7184

Bravo AF: 0.295

Asia WGS AF: 0.318 AC: 1106 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	2.4
DANN	Benign	0.72

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: rs157582; hg19: chr19-45396219; COSMIC: COSV52978582; COSMIC: COSV52978582;