dbSNP rs71352238: TOMM40:c.-9-328T>C (chr19-44891079-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000589253.1(TOMM40):c.-9-328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 217,226 control chromosomes in the GnomAD database, including 1,713 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 0.11 ( 1080 hom., cov: 33)

Exomes 𝑓: 0.13 ( 633 hom. )

Consequence

TOMM40
ENST00000589253.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.711

Publications

64 publications found

Variant links:

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]

TOMM40 links:

ENSG00000267282 (HGNC:56209):

ENSG00000267282 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2 link	c.-337T>C		upstream_gene_variant		ENST00000426677.7	NP_001122389.1	O96008-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7 link	c.-337T>C		upstream_gene_variant		1	NM_001128917.2	ENSP00000410339.1		O96008-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16002

AN:

152160

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.0924

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.0813

GnomAD4 exome

AF:

0.130

AC:

8474

AN:

64946

Hom.:

633

AF XY:

0.131

AC XY:

4304

AN XY:

32950

show subpopulations

African (AFR)

AF:

0.0209

AC:

AN:

2200

American (AMR)

AF:

0.0815

AC:

143

AN:

1754

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

257

AN:

2558

East Asian (EAS)

AF:

0.136

AC:

705

AN:

5176

South Asian (SAS)

AF:

0.111

AC:

AN:

676

European-Finnish (FIN)

AF:

0.178

AC:

963

AN:

5424

Middle Eastern (MID)

AF:

0.0381

AC:

AN:

420

European-Non Finnish (NFE)

AF:

0.138

AC:

5811

AN:

42182

Other (OTH)

AF:

0.101

AC:

458

AN:

4556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.105

AC:

16024

AN:

152280

Hom.:

1080

Cov.:

AF XY:

0.108

AC XY:

8069

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0257

AC:

1067

AN:

41592

American (AMR)

AF:

0.0934

AC:

1428

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

397

AN:

3468

East Asian (EAS)

AF:

0.109

AC:

563

AN:

5174

South Asian (SAS)

AF:

0.119

AC:

576

AN:

4834

European-Finnish (FIN)

AF:

0.184

AC:

1948

AN:

10600

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9716

AN:

68000

Other (OTH)

AF:

0.0870

AC:

184

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

723

1446

2169

2892

3615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.116

Hom.:

1255

Bravo

AF:

0.0922

Asia WGS

AF:

0.165

AC:

572

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

5.1

(source)

DANN

Benign

0.23

PhyloP100

-0.71

PromoterAI

0.042

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over