19-44893408-G-T

Position:

• chr19-44893408-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.436-372G>T		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.436-372G>T		intron_variant		1	NM_001128917.2	ENSP00000410339	P1

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.211

Alfa AF: 0.181 Hom.: 1881

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

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: rs59007384; hg19: chr19-45396665;