rs71352238

Positions:

• chr19-44891079-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000589253.1(TOMM40):​c.-9-328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 217,226 control chromosomes in the GnomAD database, including 1,713 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 0.11 (1080 hom., cov: 33)
  • Exomes 𝑓: 0.13 (633 hom.)
• Consequence: TOMM40 ENST00000589253.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.44891079T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000589253.1	c.-9-328T>C		intron_variant		3		ENSP00000465611.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16002 AN: 152160 Hom.: 1073 Cov.: 33

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0924

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.130 AC: 8474 AN: 64946 Hom.: 633 AF XY: 0.131 AC XY: 4304 AN XY: 32950

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.0815

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.105 AC: 16024 AN: 152280 Hom.: 1080 Cov.: 33 AF XY: 0.108 AC XY: 8069 AN XY: 74458

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0934

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.130 Hom.: 606

Bravo AF: 0.0922

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Benign	0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71352238; hg19: chr19-45394336;