rs2075650

Positions:

• chr19-44892362-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.275-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,608,116 control chromosomes in the GnomAD database, including 16,065 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 0.13 (1342 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14723 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.275-31A>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.275-31A>G		intron_variant		1	NM_001128917.2	ENSP00000410339	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20043 AN: 151888 Hom.: 1333 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.0970

GnomAD3 exomes AF: 0.129 AC: 32485 AN: 251370 Hom.: 2148 AF XY: 0.129 AC XY: 17530 AN XY: 135868

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0978

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0865

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.141 AC: 205242 AN: 1456110 Hom.: 14723 Cov.: 30 AF XY: 0.141 AC XY: 101870 AN XY: 724748

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.0984

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.132 AC: 20086 AN: 152006 Hom.: 1342 Cov.: 32 AF XY: 0.133 AC XY: 9904 AN XY: 74288

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.103

Alfa AF: 0.129 Hom.: 3069

Bravo AF: 0.124

Asia WGS AF: 0.172 AC: 598 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	2.5
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2075650; hg19: chr19-45395619; COSMIC: COSV52977687; COSMIC: COSV52977687;