rs78245864

Variant names:

• chr19-44891936-A-C
• rs78245864
• NM_001128917.2:c.274+247A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128917.2(TOMM40):​c.274+247A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 152,312 control chromosomes in the GnomAD database, including 78 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 0.016 (78 hom., cov: 32)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.274+247A>C		intron_variant	Intron 1 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.274+247A>C		intron_variant	Intron 1 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2436 AN: 152194 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00831

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0160 AC: 2435 AN: 152312 Hom.: 78 Cov.: 32 AF XY: 0.0177 AC XY: 1317 AN XY: 74482

African (AFR) AF: 0.00303 AC: 126 AN: 41570

American (AMR) AF: 0.0916 AC: 1400 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5188

South Asian (SAS) AF: 0.0257 AC: 124 AN: 4828

European-Finnish (FIN) AF: 0.00216 AC: 23 AN: 10626

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00831 AC: 565 AN: 68018

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0115 Hom.: 6

Bravo AF: 0.0229

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-0.021
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78245864; hg19: chr19-45395193;