NM_001128917.2:c.644-63C>T

Variant names:

• chr19-44900667-C-T
• rs1160984
• NM_001128917.2:c.644-63C>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.644-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 1,610,400 control chromosomes in the GnomAD database, including 2,566 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 0.040 (163 hom., cov: 33)
  • Exomes 𝑓: 0.054 (2403 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 12 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-63C>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.644-63C>T		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6024 AN: 152170 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0545 AC: 79397 AN: 1458112 Hom.: 2403 AF XY: 0.0556 AC XY: 40357 AN XY: 725394

African (AFR) AF: 0.00860 AC: 287 AN: 33386

American (AMR) AF: 0.0302 AC: 1346 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 1893 AN: 26074

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39638

South Asian (SAS) AF: 0.0774 AC: 6648 AN: 85872

European-Finnish (FIN) AF: 0.0268 AC: 1425 AN: 53266

Middle Eastern (MID) AF: 0.0814 AC: 336 AN: 4130

European-Non Finnish (NFE) AF: 0.0579 AC: 64363 AN: 1111018

Other (OTH) AF: 0.0514 AC: 3092 AN: 60122

GnomAD4 genome AF: 0.0396 AC: 6025 AN: 152288 Hom.: 163 Cov.: 33 AF XY: 0.0382 AC XY: 2848 AN XY: 74470

African (AFR) AF: 0.0102 AC: 425 AN: 41574

American (AMR) AF: 0.0389 AC: 595 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0745 AC: 360 AN: 4830

European-Finnish (FIN) AF: 0.0235 AC: 250 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3966 AN: 67980

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0458 Hom.: 47

Bravo AF: 0.0373

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.91
PhyloP100		0.45
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: rs1160984; hg19: chr19-45403924;