22-38682018-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020243.5(TOMM22):ā€‹c.40C>Gā€‹(p.Gln14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

TOMM22
NM_020243.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.548
Variant links:
Genes affected
TOMM22 (HGNC:18002): (translocase of outer mitochondrial membrane 22) The protein encoded by this gene is an integral membrane protein of the mitochondrial outer membrane. The encoded protein interacts with TOMM20 and TOMM40, and forms a complex with several other proteins to import cytosolic preproteins into the mitochondrion. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.01958114).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TOMM22NM_020243.5 linkuse as main transcriptc.40C>G p.Gln14Glu missense_variant 1/4 ENST00000216034.6 NP_064628.1 Q9NS69Q549C5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TOMM22ENST00000216034.6 linkuse as main transcriptc.40C>G p.Gln14Glu missense_variant 1/41 NM_020243.5 ENSP00000216034.4 Q9NS69

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152272
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458944
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725650
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 25, 2024The c.40C>G (p.Q14E) alteration is located in exon 1 (coding exon 1) of the TOMM22 gene. This alteration results from a C to G substitution at nucleotide position 40, causing the glutamine (Q) at amino acid position 14 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.063
DANN
Benign
0.59
DEOGEN2
Benign
0.061
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0012
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.14
N
REVEL
Benign
0.010
Sift
Benign
0.81
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.095
MutPred
0.084
Gain of glycosylation at P13 (P = 0.052);
MVP
0.068
MPC
0.86
ClinPred
0.059
T
GERP RS
-4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.069
gMVP
0.14

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1440857430; hg19: chr22-39078023; API