NM_001128917.2:c.435+33C>T

Variant names:

• chr19-44892962-C-T
• rs157582
• NM_001128917.2:c.435+33C>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.435+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,560,052 control chromosomes in the GnomAD database, including 43,042 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 0.29 (7124 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35918 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 123 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	NM_001128917.2	MANE Select	c.435+33C>T		intron	N/A	NP_001122389.1
	TOMM40	NM_001128916.2		c.435+33C>T		intron	N/A	NP_001122388.1
	TOMM40	NM_006114.3		c.435+33C>T		intron	N/A	NP_006105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.435+33C>T		intron	N/A	ENSP00000410339.1
	TOMM40	ENST00000252487.9	TSL:1	c.435+33C>T		intron	N/A	ENSP00000252487.4
	TOMM40	ENST00000405636.6	TSL:1	c.435+33C>T		intron	N/A	ENSP00000385184.2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43266 AN: 151914 Hom.: 7092 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.239

GnomAD2 exomes AF: 0.240 AC: 54992 AN: 229254 AF XY: 0.230

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.222 AC: 312343 AN: 1408020 Hom.: 35918 Cov.: 23 AF XY: 0.219 AC XY: 153778 AN XY: 700788

African (AFR) AF: 0.475 AC: 15323 AN: 32260

American (AMR) AF: 0.279 AC: 11722 AN: 42044

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5075 AN: 25040

East Asian (EAS) AF: 0.222 AC: 8719 AN: 39210

South Asian (SAS) AF: 0.183 AC: 15209 AN: 83242

European-Finnish (FIN) AF: 0.231 AC: 12177 AN: 52664

Middle Eastern (MID) AF: 0.159 AC: 893 AN: 5634

European-Non Finnish (NFE) AF: 0.215 AC: 230314 AN: 1069422

Other (OTH) AF: 0.221 AC: 12911 AN: 58504

GnomAD4 genome AF: 0.285 AC: 43360 AN: 152032 Hom.: 7124 Cov.: 32 AF XY: 0.286 AC XY: 21282 AN XY: 74314

African (AFR) AF: 0.461 AC: 19118 AN: 41442

American (AMR) AF: 0.264 AC: 4025 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5164

South Asian (SAS) AF: 0.195 AC: 938 AN: 4800

European-Finnish (FIN) AF: 0.224 AC: 2374 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14442 AN: 67986

Other (OTH) AF: 0.245 AC: 518 AN: 2114

Alfa AF: 0.235 Hom.: 19283

Bravo AF: 0.295

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		0.015
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: rs157582; hg19: chr19-45396219; COSMIC: COSV52978582; COSMIC: COSV52978582;