Variant 17-58305398-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000343736.9(TSPOAP1):c.5422G>A(p.Gly1808Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TSPOAP1
ENST00000343736.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 7.65

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 links:

Genome browser will be placed here

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, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPOAP1	NM_004758.4 linkuse as main transcript	c.5422G>A	p.Gly1808Ser	missense_variant	29/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.5395G>A	p.Gly1799Ser	missense_variant	29/32		NP_001248764.1
TSPOAP1	NM_024418.3 linkuse as main transcript	c.5242G>A	p.Gly1748Ser	missense_variant	28/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9 linkuse as main transcript	c.5422G>A	p.Gly1808Ser	missense_variant	29/32	1	NM_004758.4	ENSP00000345824	P2	O95153-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251254

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135784

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonia 22, adult-onset

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 31, 2023

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TSPOAP1: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.046

.;.;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.073

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.7

.;.;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.9

.;D;.;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.010

.;D;.;D

Sift4G

Pathogenic

0.0

D;D;.;D

Polyphen

1.0

.;D;.;D

Vest4

0.88, 0.90

MutPred

0.70

.;.;.;Loss of loop (P = 0.0804);

MVP

0.72

MPC

0.80

ClinPred

0.86

GERP RS

4.4

Varity_R

0.75

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over