Genetic Variant TOMM20:c.-339G>C (chr1-235129054-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014765.3(TOMM20):c.-339G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 302,458 control chromosomes in the GnomAD database, including 16,050 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 0.26 ( 6559 hom., cov: 33)

Exomes 𝑓: 0.34 ( 9491 hom. )

Consequence

TOMM20
NM_014765.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.01

Variant links:

Genes affected

TOMM20 (HGNC:20947): (translocase of outer mitochondrial membrane 20) Enables protein-transporting ATPase activity and unfolded protein binding activity. Involved in protein targeting to mitochondrion. Located in mitochondria-associated endoplasmic reticulum membrane and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

TOMM20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20	NM_014765.3 link	c.-339G>C		upstream_gene_variant		ENST00000366607.5	NP_055580.1	Q15388A0A024R3W2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM20	ENST00000366607.5 link	c.-339G>C		upstream_gene_variant		1	NM_014765.3	ENSP00000355566.4		Q15388

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39886

AN:

152036

Hom.:

6565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0689

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.338

AC:

50754

AN:

150304

Hom.:

9491

AF XY:

0.355

AC XY:

28503

AN XY:

80194

show subpopulations

Gnomad4 AFR exome

AF:

0.0599

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.515

Gnomad4 FIN exome

AF:

0.350

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.262

AC:

39879

AN:

152154

Hom.:

6559

Cov.:

AF XY:

0.270

AC XY:

20063

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0689

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.326

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.170

Hom.:

407

Bravo

AF:

0.247

Asia WGS

AF:

0.365

AC:

1267

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.51

DANN

Benign

0.46

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over