rs1160985

Variant names:

• chr19-44900155-C-T
• rs1160985
• NM_001128917.2:c.644-575C>T

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,904 control chromosomes in the GnomAD database, including 20,520 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 0.51 (20520 hom., cov: 31)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-575C>T		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.644-575C>T		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77672 AN: 151786 Hom.: 20502 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.512 AC: 77741 AN: 151904 Hom.: 20520 Cov.: 31 AF XY: 0.512 AC XY: 38017 AN XY: 74224

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.528

Alfa AF: 0.464 Hom.: 30210

Bravo AF: 0.520

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.066
DANN	Benign	0.43

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: rs1160985; hg19: chr19-45403412;