rs1160983

Positions:

• chr19-44893972-G-A

Variant summary

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

The NM_001128917.2(TOMM40):​c.549G>A​(p.Ser183Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 1,559,834 control chromosomes in the GnomAD database, including 1,117 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 0.048 (256 hom., cov: 32)
  • Exomes 𝑓: 0.032 (861 hom.)
• Consequence: TOMM40 NM_001128917.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.39

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=-0.57).
• BP7: Synonymous conserved (PhyloP=-6.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.549G>A	p.Ser183Ser	synonymous_variant	5/9	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.549G>A	p.Ser183Ser	synonymous_variant	5/9	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7246 AN: 152140 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0502

GnomAD3 exomes AF: 0.0354 AC: 7442 AN: 209954 Hom.: 208 AF XY: 0.0331 AC XY: 3715 AN XY: 112306

Gnomad AFR exome AF: 0.0889

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0433

Gnomad EAS exome AF: 0.0736

Gnomad SAS exome AF: 0.00904

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0331

GnomAD4 exome AF: 0.0316 AC: 44531 AN: 1407576 Hom.: 861 Cov.: 32 AF XY: 0.0309 AC XY: 21445 AN XY: 694134

Gnomad4 AFR exome AF: 0.0888

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0410

Gnomad4 EAS exome AF: 0.0628

Gnomad4 SAS exome AF: 0.00774

Gnomad4 FIN exome AF: 0.0197

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0327

GnomAD4 genome AF: 0.0476 AC: 7250 AN: 152258 Hom.: 256 Cov.: 32 AF XY: 0.0467 AC XY: 3477 AN XY: 74446

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0436 Hom.: 57

Bravo AF: 0.0501

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.4
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1160983; hg19: chr19-45397229; COSMIC: COSV52977056; COSMIC: COSV52977056;