rs157590

Variant names:

• chr19-44895459-A-C
• rs157590
• NM_001128917.2:c.643+1393A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-44895459-A-C
• chr19-44895459-A-G

Variant summary

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

The NM_001128917.2(TOMM40):​c.643+1393A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,798 control chromosomes in the GnomAD database, including 28,236 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 0.59 (28236 hom., cov: 30)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.643+1393A>C		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.643+1393A>C		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89261 AN: 151680 Hom.: 28191 Cov.: 30

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.589 AC: 89369 AN: 151798 Hom.: 28236 Cov.: 30 AF XY: 0.588 AC XY: 43614 AN XY: 74146

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.586

Alfa AF: 0.541 Hom.: 8904

Bravo AF: 0.605

Asia WGS AF: 0.436 AC: 1519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.69

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: rs157590; hg19: chr19-45398716;