19-44899959-C-T

Variant names:

• chr19-44899959-C-T
• rs115881343
• NM_001128917.2:c.644-771C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001128917.2(TOMM40):​c.644-771C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 151,838 control chromosomes in the GnomAD database, including 62 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 0.028 (62 hom., cov: 30)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 21 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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0281 (4274/151838) while in subpopulation AFR AF = 0.0427 (1770/41426). AF 95% confidence interval is 0.0411. There are 62 homozygotes in GnomAd4. There are 2062 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4274 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-771C>T		intron_variant	Intron 5 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-771C>T		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4268 AN: 151722 Hom.: 60 Cov.: 30

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0197

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

GnomAD4 genome AF: 0.0281 AC: 4274 AN: 151838 Hom.: 62 Cov.: 30 AF XY: 0.0278 AC XY: 2062 AN XY: 74220

African (AFR) AF: 0.0427 AC: 1770 AN: 41426

American (AMR) AF: 0.0123 AC: 188 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3466

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5162

South Asian (SAS) AF: 0.0244 AC: 117 AN: 4794

European-Finnish (FIN) AF: 0.0238 AC: 251 AN: 10542

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0263 AC: 1786 AN: 67908

Other (OTH) AF: 0.0194 AC: 41 AN: 2108

Alfa AF: 0.0311 Hom.: 24

Bravo AF: 0.0285

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.82
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism

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: rs115881343; hg19: chr19-45403216;