1-235129054-C-G

Variant names:

• chr1-235129054-C-G
• rs17523127
• NM_014765.3:c.-339G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.-339G>C		upstream_gene_variant		ENST00000366607.5	NP_055580.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39886 AN: 152036 Hom.: 6565 Cov.: 33

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

African (AFR) AF: 0.0599 AC: 240 AN: 4004

American (AMR) AF: 0.383 AC: 2123 AN: 5542

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 1112 AN: 4162

East Asian (EAS) AF: 0.233 AC: 1603 AN: 6882

South Asian (SAS) AF: 0.515 AC: 11604 AN: 22534

European-Finnish (FIN) AF: 0.350 AC: 2792 AN: 7966

Middle Eastern (MID) AF: 0.282 AC: 190 AN: 674

European-Non Finnish (NFE) AF: 0.316 AC: 28464 AN: 90030

Other (OTH) AF: 0.309 AC: 2626 AN: 8510

GnomAD4 genome AF: 0.262 AC: 39879 AN: 152154 Hom.: 6559 Cov.: 33 AF XY: 0.270 AC XY: 20063 AN XY: 74368

African (AFR) AF: 0.0689 AC: 2862 AN: 41544

American (AMR) AF: 0.358 AC: 5475 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1206 AN: 5172

South Asian (SAS) AF: 0.527 AC: 2545 AN: 4826

European-Finnish (FIN) AF: 0.364 AC: 3846 AN: 10570

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22137 AN: 67982

Other (OTH) AF: 0.263 AC: 553 AN: 2104

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
PhyloP100		-3.0
PromoterAI		0.0033	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17523127; hg19: chr1-235292369;