rs34404554

chr19-44892652-C-Gchr19-44892652-C-T

Variant summary

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

The NM_001128917.2(TOMM40):c.343-185C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,176 control chromosomes in the GnomAD database, including 1,193 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 0.12 (1193 hom., cov: 32)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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=-0.85).
• 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	UniProt
TOMM40	NM_001128917.2	c.343-185C>G		intron_variant		ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7	c.343-185C>G		intron_variant		1	NM_001128917.2	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18652 AN: 152058 Hom.: 1185 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.0915

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

GnomAD4 genome AF: 0.123 AC: 18692 AN: 152176 Hom.: 1193 Cov.: 32 AF XY: 0.125 AC XY: 9292 AN XY: 74386

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.0972

Alfa AF: 0.0734 Hom.: 90

Bravo AF: 0.114

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.2
Dann	Benign	0.59

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: rs34404554; hg19: chr19-45395909;