Variant 17-58310100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000343736.9(TSPOAP1):c.3758G>A(p.Arg1253His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,613,380 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1253C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 13 hom. )

Consequence

TSPOAP1
ENST00000343736.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.20

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075471997).

BP6

Variant 17-58310100-C-T is Benign according to our data. Variant chr17-58310100-C-T is described in ClinVar as [Benign]. Clinvar id is 713165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPOAP1	NM_004758.4 linkuse as main transcript	c.3758G>A	p.Arg1253His	missense_variant	21/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.3758G>A	p.Arg1253His	missense_variant	21/32		NP_001248764.1
TSPOAP1	NM_024418.3 linkuse as main transcript	c.3578G>A	p.Arg1193His	missense_variant	20/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9 linkuse as main transcript	c.3758G>A	p.Arg1253His	missense_variant	21/32	1	NM_004758.4	ENSP00000345824	P2	O95153-1
TSPOAP1	ENST00000268893.10 linkuse as main transcript	c.3578G>A	p.Arg1193His	missense_variant	20/31	1		ENSP00000268893	A2	O95153-2
TSPOAP1	ENST00000580669.6 linkuse as main transcript	c.1154G>A	p.Arg385His	missense_variant	5/16	5		ENSP00000462822
TSPOAP1	ENST00000582679.1 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	2/6	5		ENSP00000462710

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00540

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00151

AC:

370

AN:

245802

Hom.:

AF XY:

0.00188

AC XY:

250

AN XY:

133246

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00398

Gnomad SAS exome

AF:

0.00942

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000715

AC:

1045

AN:

1461046

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

685

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00156

Gnomad4 SAS exome

AF:

0.00934

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.000597

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00522

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000415

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.00178

AC:

216

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	TSPOAP1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.071

.;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Uncertain

0.44

MutationAssessor

Uncertain

2.3

.;.;M

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.1

D;.;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.020

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.63

MVP

0.87

MPC

0.88

ClinPred

0.11

GERP RS

5.0

Varity_R

0.46

gMVP

0.54

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.

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