19-44892887-C-T

Position:

• chr19-44892887-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001128917.2(TOMM40):​c.393C>T​(p.Phe131Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,380 control chromosomes in the GnomAD database, including 15,939 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 (1265 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14674 hom.)
• Consequence: TOMM40 NM_001128917.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=-0.945 with no splicing effect.
• 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.393C>T	p.Phe131Phe	synonymous_variant	3/9	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.393C>T	p.Phe131Phe	synonymous_variant	3/9	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19320 AN: 152064 Hom.: 1257 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.0933

GnomAD3 exomes AF: 0.128 AC: 32087 AN: 250946 Hom.: 2095 AF XY: 0.128 AC XY: 17358 AN XY: 135634

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0972

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0866

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.140 AC: 205087 AN: 1461198 Hom.: 14674 Cov.: 32 AF XY: 0.140 AC XY: 101775 AN XY: 726914

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0974

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: 0.124

GnomAD4 genome AF: 0.127 AC: 19362 AN: 152182 Hom.: 1265 Cov.: 32 AF XY: 0.129 AC XY: 9591 AN XY: 74374

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.105 Hom.: 614

Bravo AF: 0.119

Asia WGS AF: 0.171 AC: 596 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.9
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs11556505; hg19: chr19-45396144;