19-44893408-G-T

Variant names:

• chr19-44893408-G-T
• rs59007384
• NM_001128917.2:c.436-372G>T

Variant summary

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

The NM_001128917.2(TOMM40):​c.436-372G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,086 control chromosomes in the GnomAD database, including 4,206 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 0.23 (4206 hom., cov: 32)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 68 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.436-372G>T		intron_variant	Intron 3 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.436-372G>T		intron_variant	Intron 3 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35106 AN: 151968 Hom.: 4179 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35191 AN: 152086 Hom.: 4206 Cov.: 32 AF XY: 0.234 AC XY: 17425 AN XY: 74350

African (AFR) AF: 0.293 AC: 12149 AN: 41488

American (AMR) AF: 0.242 AC: 3693 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5166

South Asian (SAS) AF: 0.196 AC: 948 AN: 4828

European-Finnish (FIN) AF: 0.221 AC: 2334 AN: 10572

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.201 AC: 13648 AN: 67962

Other (OTH) AF: 0.211 AC: 447 AN: 2114

Alfa AF: 0.208 Hom.: 7436

Bravo AF: 0.233

Asia WGS AF: 0.318 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		0.098
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: rs59007384; hg19: chr19-45396665;