19-44892457-T-C

Position:

• chr19-44892457-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001128917.2(TOMM40):​c.339T>C​(p.Phe113Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,611,534 control chromosomes in the GnomAD database, including 46,154 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 0.29 (7174 hom., cov: 31)
  • Exomes 𝑓: 0.23 (38980 hom.)
• Consequence: TOMM40 NM_001128917.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.339T>C	p.Phe113Phe	synonymous_variant	2/9	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.339T>C	p.Phe113Phe	synonymous_variant	2/9	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43614 AN: 151764 Hom.: 7146 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.241

GnomAD3 exomes AF: 0.246 AC: 61815 AN: 251406 Hom.: 8162 AF XY: 0.237 AC XY: 32168 AN XY: 135876

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.210

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.227 AC: 331325 AN: 1459652 Hom.: 38980 Cov.: 33 AF XY: 0.225 AC XY: 163564 AN XY: 726170

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.288 AC: 43704 AN: 151882 Hom.: 7174 Cov.: 31 AF XY: 0.289 AC XY: 21480 AN XY: 74228

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.248

Alfa AF: 0.226 Hom.: 5219

Bravo AF: 0.297

Asia WGS AF: 0.334 AC: 1162 AN: 3478

EpiCase AF: 0.206

EpiControl AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.82

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: rs157581; hg19: chr19-45395714; COSMIC: COSV52976179; COSMIC: COSV52976179;