rs1160985

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 74 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.644 AC: 26687 AN: 41434

American (AMR) AF: 0.535 AC: 8166 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1614 AN: 5164

South Asian (SAS) AF: 0.402 AC: 1935 AN: 4808

European-Finnish (FIN) AF: 0.510 AC: 5366 AN: 10522

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30603 AN: 67938

Other (OTH) AF: 0.528 AC: 1111 AN: 2106

Alfa AF: 0.470 Hom.: 70369

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
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1160985; hg19: chr19-45403412;