rs760136

chr19-44900601-A-G

Variant summary

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

The NM_001128917.2(TOMM40):c.644-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,553,622 control chromosomes in the GnomAD database, including 159,705 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 (20553 hom., cov: 32)
  • Exomes 𝑓: 0.44 (139152 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-0.92).
• 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	UniProt
TOMM40	NM_001128917.2	c.644-129A>G		intron_variant		ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-129A>G		intron_variant		1	NM_001128917.2	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77751 AN: 151932 Hom.: 20535 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.442 AC: 619022 AN: 1401572 Hom.: 139152 AF XY: 0.440 AC XY: 306611 AN XY: 696836

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.512 AC: 77820 AN: 152050 Hom.: 20553 Cov.: 32 AF XY: 0.512 AC XY: 38063 AN XY: 74328

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.528

Alfa AF: 0.497 Hom.: 3433

Bravo AF: 0.520

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.3
Dann	Benign	0.19

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: rs760136; hg19: chr19-45403858;