rs10119

Positions:

• chr19-44903416-G-A

Variant summary

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

The NM_001128917.2(TOMM40):​c.*247G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 411,388 control chromosomes in the GnomAD database, including 16,271 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 0.28 (6132 hom., cov: 33)
  • Exomes 𝑓: 0.27 (10139 hom.)
• Consequence: TOMM40 NM_001128917.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.*247G>A		3_prime_UTR_variant	9/9	ENST00000426677.7	NP_001122389.1
TOMM40	NM_001128916.2	c.*247G>A		3_prime_UTR_variant	10/10		NP_001122388.1
TOMM40	NM_006114.3	c.*247G>A		3_prime_UTR_variant	10/10		NP_006105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.*247G>A		3_prime_UTR_variant	9/9	1	NM_001128917.2	ENSP00000410339.1
TOMM40	ENST00000252487.9	c.*247G>A		3_prime_UTR_variant	10/10	1		ENSP00000252487.4
TOMM40	ENST00000405636.6	c.*247G>A		3_prime_UTR_variant	10/10	1		ENSP00000385184.2
TOMM40	ENST00000592434.5	c.*2062G>A		3_prime_UTR_variant	9/9	2		ENSP00000466084.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42369 AN: 152058 Hom.: 6105 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.273 AC: 70647 AN: 259212 Hom.: 10139 Cov.: 4 AF XY: 0.271 AC XY: 36891 AN XY: 136076

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.279 AC: 42455 AN: 152176 Hom.: 6132 Cov.: 33 AF XY: 0.277 AC XY: 20581 AN XY: 74380

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.263

Alfa AF: 0.294 Hom.: 849

Bravo AF: 0.275

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10119; hg19: chr19-45406673;