rs157580

chr19-44892009-G-Achr19-44892009-G-Cchr19-44892009-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.274+320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,936 control chromosomes in the GnomAD database, including 36,886 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 0.69 (36886 hom., cov: 31)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40	NM_001128917.2	c.274+320G>A		intron_variant		ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7	c.274+320G>A		intron_variant		1	NM_001128917.2	P1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104279 AN: 151818 Hom.: 36820 Cov.: 31

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.687 AC: 104414 AN: 151936 Hom.: 36886 Cov.: 31 AF XY: 0.692 AC XY: 51363 AN XY: 74276

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.656

Alfa AF: 0.617 Hom.: 62693

Bravo AF: 0.689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs157580; hg19: chr19-45395266;