rs8106922

Positions:

• chr19-44898409-A-G

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-2321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,244 control chromosomes in the GnomAD database, including 10,380 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 0.36 (10380 hom., cov: 30)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

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 (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-2321A>G		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-2321A>G		intron_variant		1	NM_001128917.2	ENSP00000410339	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54356 AN: 151148 Hom.: 10376 Cov.: 30

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.360 AC: 54380 AN: 151244 Hom.: 10380 Cov.: 30 AF XY: 0.363 AC XY: 26829 AN XY: 73868

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.381

Alfa AF: 0.402 Hom.: 18619

Bravo AF: 0.345

Asia WGS AF: 0.260 AC: 905 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	0.38
DANN	Benign	0.69

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: rs8106922; hg19: chr19-45401666; COSMIC: COSV52987669; COSMIC: COSV52987669;