6-41044052-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001010873.3(TSPO2):c.428C>T(p.Thr143Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
TSPO2
NM_001010873.3 missense
NM_001010873.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 2.28
Genes affected
TSPO2 (HGNC:21256): (translocator protein 2) Predicted to enable cholesterol binding activity. Involved in amino acid import across plasma membrane. Located in organelle membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
OARD1 (HGNC:21257): (O-acyl-ADP-ribose deacylase 1) The protein encoded by this gene is a deacylase that can convert O-acetyl-ADP-ribose to ADP-ribose and acetate, O-propionyl-ADP-ribose to ADP-ribose and propionate, and O-butyryl-ADP-ribose to ADP-ribose and butyrate. The ADP-ribose product is able to inhibit these reactions through a competitive feedback loop. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPO2 | NM_001010873.3 | c.428C>T | p.Thr143Ile | missense_variant | 4/4 | ENST00000373161.6 | |
TSPO2 | NM_001159726.1 | c.428C>T | p.Thr143Ile | missense_variant | 4/4 | ||
TSPO2 | XM_011514396.3 | c.428C>T | p.Thr143Ile | missense_variant | 4/4 | ||
TSPO2 | XM_011514397.3 | c.428C>T | p.Thr143Ile | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPO2 | ENST00000373161.6 | c.428C>T | p.Thr143Ile | missense_variant | 4/4 | 1 | NM_001010873.3 | P1 | |
TSPO2 | ENST00000470917.1 | c.428C>T | p.Thr143Ile | missense_variant | 4/4 | 1 | P1 | ||
TSPO2 | ENST00000373158.6 | c.*73C>T | 3_prime_UTR_variant | 3/3 | 1 | ||||
OARD1 | ENST00000482853.5 | c.*12+8213G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33
GnomAD3 genomes
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33
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74476
GnomAD4 genome
?
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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 | Aug 17, 2022 | The c.428C>T (p.T143I) alteration is located in exon 4 (coding exon 3) of the TSPO2 gene. This alteration results from a C to T substitution at nucleotide position 428, causing the threonine (T) at amino acid position 143 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Gain of catalytic residue at L148 (P = 0.045);Gain of catalytic residue at L148 (P = 0.045);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.