rs760136

Variant names:

• chr19-44900601-A-G
• rs760136
• NM_001128917.2:c.644-129A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128917.2(TOMM40):​c.644-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,553,622 control chromosomes in the GnomAD database, including 159,705 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 (20553 hom., cov: 32)
  • Exomes 𝑓: 0.44 (139152 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 22 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=-0.92).
• 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.644-129A>G		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.644-129A>G		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77751 AN: 151932 Hom.: 20535 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.442 AC: 619022 AN: 1401572 Hom.: 139152 AF XY: 0.440 AC XY: 306611 AN XY: 696836

African (AFR) AF: 0.643 AC: 20090 AN: 31220

American (AMR) AF: 0.572 AC: 19327 AN: 33802

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 11591 AN: 24358

East Asian (EAS) AF: 0.305 AC: 11650 AN: 38240

South Asian (SAS) AF: 0.400 AC: 32366 AN: 80954

European-Finnish (FIN) AF: 0.501 AC: 24847 AN: 49598

Middle Eastern (MID) AF: 0.469 AC: 1852 AN: 3952

European-Non Finnish (NFE) AF: 0.436 AC: 471930 AN: 1081624

Other (OTH) AF: 0.439 AC: 25369 AN: 57824

GnomAD4 genome AF: 0.512 AC: 77820 AN: 152050 Hom.: 20553 Cov.: 32 AF XY: 0.512 AC XY: 38063 AN XY: 74328

African (AFR) AF: 0.644 AC: 26716 AN: 41476

American (AMR) AF: 0.535 AC: 8174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1627 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1617 AN: 5166

South Asian (SAS) AF: 0.402 AC: 1935 AN: 4816

European-Finnish (FIN) AF: 0.510 AC: 5395 AN: 10580

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.450 AC: 30608 AN: 67946

Other (OTH) AF: 0.528 AC: 1117 AN: 2114

Alfa AF: 0.501 Hom.: 4089

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	-0.92
CADD	Benign	1.3
DANN	Benign	0.19
PhyloP100		-1.5
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: rs760136; hg19: chr19-45403858;