19-44901434-A-G

Variant summary

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

The NM_001128917.2(TOMM40):​c.946+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,494,492 control chromosomes in the GnomAD database, including 397,046 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 0.76 ( 45120 hom., cov: 34)
Exomes 𝑓: 0.72 ( 351926 hom. )

Consequence

TOMM40
NM_001128917.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Publications

48 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]

Genome browser will be placed here

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=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOMM40NM_001128917.2 linkc.946+124A>G intron_variant Intron 8 of 8 ENST00000426677.7 NP_001122389.1 O96008-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOMM40ENST00000426677.7 linkc.946+124A>G intron_variant Intron 8 of 8 1 NM_001128917.2 ENSP00000410339.1 O96008-1

Frequencies

GnomAD3 genomes
AF:
0.764
AC:
116208
AN:
152096
Hom.:
45058
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.876
Gnomad AMI
AF:
0.796
Gnomad AMR
AF:
0.728
Gnomad ASJ
AF:
0.811
Gnomad EAS
AF:
0.428
Gnomad SAS
AF:
0.648
Gnomad FIN
AF:
0.788
Gnomad MID
AF:
0.788
Gnomad NFE
AF:
0.731
Gnomad OTH
AF:
0.755
GnomAD4 exome
AF:
0.721
AC:
968433
AN:
1342278
Hom.:
351926
Cov.:
52
AF XY:
0.720
AC XY:
471340
AN XY:
654762
show subpopulations
African (AFR)
AF:
0.882
AC:
26668
AN:
30234
American (AMR)
AF:
0.741
AC:
22035
AN:
29718
Ashkenazi Jewish (ASJ)
AF:
0.806
AC:
17318
AN:
21484
East Asian (EAS)
AF:
0.448
AC:
15745
AN:
35144
South Asian (SAS)
AF:
0.654
AC:
46546
AN:
71182
European-Finnish (FIN)
AF:
0.785
AC:
35646
AN:
45382
Middle Eastern (MID)
AF:
0.773
AC:
4167
AN:
5394
European-Non Finnish (NFE)
AF:
0.726
AC:
761012
AN:
1048312
Other (OTH)
AF:
0.709
AC:
39296
AN:
55428
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
14410
28820
43229
57639
72049
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
19588
39176
58764
78352
97940
<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:
0.764
AC:
116336
AN:
152214
Hom.:
45120
Cov.:
34
AF XY:
0.764
AC XY:
56850
AN XY:
74422
show subpopulations
African (AFR)
AF:
0.876
AC:
36409
AN:
41554
American (AMR)
AF:
0.728
AC:
11134
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.811
AC:
2816
AN:
3472
East Asian (EAS)
AF:
0.429
AC:
2214
AN:
5166
South Asian (SAS)
AF:
0.649
AC:
3129
AN:
4818
European-Finnish (FIN)
AF:
0.788
AC:
8357
AN:
10604
Middle Eastern (MID)
AF:
0.779
AC:
229
AN:
294
European-Non Finnish (NFE)
AF:
0.731
AC:
49727
AN:
68000
Other (OTH)
AF:
0.757
AC:
1598
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1413
2827
4240
5654
7067
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
850
1700
2550
3400
4250
<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:
0.749
Hom.:
42886
Bravo
AF:
0.763
Asia WGS
AF:
0.624
AC:
2170
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
12
DANN
Benign
0.21
PhyloP100
-2.3
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs405697; hg19: chr19-45404691; COSMIC: COSV52986417; COSMIC: COSV52986417; API