NM_001128917.2:c.*247G>A

Variant names:

• chr19-44903416-G-A
• rs10119
• NM_001128917.2:c.*247G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 97 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.*247G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000426677.7	NP_001122389.1
TOMM40	NM_001128916.2	c.*247G>A		3_prime_UTR_variant	Exon 10 of 10		NP_001122388.1
TOMM40	NM_006114.3	c.*247G>A		3_prime_UTR_variant	Exon 10 of 10		NP_006105.1

Ensembl

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

African (AFR) AF: 0.335 AC: 2088 AN: 6232

American (AMR) AF: 0.191 AC: 1258 AN: 6602

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 2693 AN: 8192

East Asian (EAS) AF: 0.160 AC: 2310 AN: 14482

South Asian (SAS) AF: 0.257 AC: 7704 AN: 30012

European-Finnish (FIN) AF: 0.289 AC: 4859 AN: 16830

Middle Eastern (MID) AF: 0.330 AC: 394 AN: 1194

European-Non Finnish (NFE) AF: 0.281 AC: 45179 AN: 160512

Other (OTH) AF: 0.275 AC: 4162 AN: 15156

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

African (AFR) AF: 0.328 AC: 13626 AN: 41536

American (AMR) AF: 0.206 AC: 3157 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3472

East Asian (EAS) AF: 0.114 AC: 588 AN: 5150

South Asian (SAS) AF: 0.247 AC: 1192 AN: 4828

European-Finnish (FIN) AF: 0.271 AC: 2870 AN: 10592

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18958 AN: 67984

Other (OTH) AF: 0.263 AC: 555 AN: 2114

Alfa AF: 0.177 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
PhyloP100		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10119; hg19: chr19-45406673;