17-58327896-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.25C>T​(p.Arg9Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,602,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.902
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]
TSPOAP1-AS1 (HGNC:44148): (TSPOAP1, SUPT4H1 and RNF43 antisense RNA 1)

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=0.07192677).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSPOAP1NM_004758.4 linkc.25C>T p.Arg9Trp missense_variant 1/32 ENST00000343736.9 NP_004749.2 O95153-1B7ZVZ7B2RUT8A7E2C5
TSPOAP1NM_001261835.2 linkc.25C>T p.Arg9Trp missense_variant 1/32 NP_001248764.1 O95153B7ZVZ7X5DQQ3A7E2C5
TSPOAP1NM_024418.3 linkc.25C>T p.Arg9Trp missense_variant 1/31 NP_077729.1 O95153-2B7ZVZ7B2RUT8
TSPOAP1-AS1NR_038410.1 linkn.280-154G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSPOAP1ENST00000343736.9 linkc.25C>T p.Arg9Trp missense_variant 1/321 NM_004758.4 ENSP00000345824.4 O95153-1

Frequencies

GnomAD3 genomes
AF:
0.0000985
AC:
15
AN:
152234
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000812
AC:
20
AN:
246156
Hom.:
0
AF XY:
0.0000897
AC XY:
12
AN XY:
133746
show subpopulations
Gnomad AFR exome
AF:
0.000380
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.0000658
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000994
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000113
AC:
164
AN:
1450446
Hom.:
0
Cov.:
31
AF XY:
0.000114
AC XY:
82
AN XY:
719182
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.0000674
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000131
Gnomad4 OTH exome
AF:
0.000151
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152352
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.000168
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000136
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterresearchSN ONGC Dept of Genetics and Molecular biology Vision Research Foundation-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.037
.;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.063
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.020
D;D
Polyphen
0.99
D;D
Vest4
0.22
MVP
0.61
MPC
0.58
ClinPred
0.081
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.094
gMVP
0.15

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: rs150941874; hg19: chr17-56405257; API