1-161227663-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032174.6(TOMM40L):c.304G>A(p.Asp102Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,276 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000021 ( 1 hom. )
Consequence
TOMM40L
NM_032174.6 missense
NM_032174.6 missense
Scores
7
5
7
Clinical Significance
Conservation
PhyloP100: 9.75
Genes affected
TOMM40L (HGNC:25756): (translocase of outer mitochondrial membrane 40 like) Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.904
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TOMM40L | NM_032174.6 | c.304G>A | p.Asp102Asn | missense_variant | 5/10 | ENST00000367988.8 | NP_115550.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TOMM40L | ENST00000367988.8 | c.304G>A | p.Asp102Asn | missense_variant | 5/10 | 2 | NM_032174.6 | ENSP00000356967.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250756Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135536
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461276Hom.: 1 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 726924
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GnomAD4 genome Cov.: 32
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32
ExAC
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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 submitter | clinical testing | Ambry Genetics | May 18, 2023 | The c.304G>A (p.D102N) alteration is located in exon 5 (coding exon 4) of the TOMM40L gene. This alteration results from a G to A substitution at nucleotide position 304, causing the aspartic acid (D) at amino acid position 102 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at