17-58308621-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004758.4(TSPOAP1):​c.4651C>T​(p.Arg1551Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,448,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0680
Variant links:
Genes affected
TSPOAP1 (HGNC:16831): (TSPO associated protein 1) Enables benzodiazepine receptor binding activity. Predicted to be involved in regulation of presynaptic cytosolic calcium ion concentration. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14529562).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSPOAP1NM_004758.4 linkuse as main transcriptc.4651C>T p.Arg1551Cys missense_variant 22/32 ENST00000343736.9 NP_004749.2
TSPOAP1NM_001261835.2 linkuse as main transcriptc.4651C>T p.Arg1551Cys missense_variant 22/32 NP_001248764.1
TSPOAP1NM_024418.3 linkuse as main transcriptc.4471C>T p.Arg1491Cys missense_variant 21/31 NP_077729.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSPOAP1ENST00000343736.9 linkuse as main transcriptc.4651C>T p.Arg1551Cys missense_variant 22/321 NM_004758.4 ENSP00000345824 P2O95153-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000812
AC:
2
AN:
246394
Hom.:
0
AF XY:
0.00000748
AC XY:
1
AN XY:
133622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000901
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000138
AC:
20
AN:
1448926
Hom.:
0
Cov.:
31
AF XY:
0.0000139
AC XY:
10
AN XY:
718752
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:
0.0000117
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.0000154
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000594

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 GeneticsNov 09, 2021The c.4651C>T (p.R1551C) alteration is located in exon 22 (coding exon 22) of the TSPOAP1 gene. This alteration results from a C to T substitution at nucleotide position 4651, causing the arginine (R) at amino acid position 1551 to be replaced by a cysteine (C). 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
0.081
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.061
.;.;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.94
.;.;L
MutationTaster
Benign
0.77
D;D;D
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.4
N;.;N
REVEL
Benign
0.12
Sift
Benign
0.072
T;.;T
Sift4G
Uncertain
0.058
T;.;T
Polyphen
0.030
B;.;B
Vest4
0.18
MutPred
0.31
.;.;Gain of catalytic residue at P1550 (P = 0.0123);
MVP
0.18
MPC
0.29
ClinPred
0.30
T
GERP RS
5.2
Varity_R
0.079
gMVP
0.55

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: rs748011478; hg19: chr17-56385982; COSMIC: COSV99271538; COSMIC: COSV99271538; API