Variant chr17-58325640-C-A 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 NM_004758.4(TSPOAP1):c.644G>T(p.Arg215Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000584 in 1,613,474 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.01

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:

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

TSPOAP1-AS1 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=0.007420212).

BP6

Variant 17-58325640-C-A is Benign according to our data. Variant chr17-58325640-C-A is described in ClinVar as [Benign]. Clinvar id is 714860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPOAP1	NM_004758.4 link	c.644G>T	p.Arg215Leu	missense_variant	4/32	ENST00000343736.9	NP_004749.2	O95153-1B7ZVZ7B2RUT8A7E2C5
TSPOAP1	NM_001261835.2 link	c.644G>T	p.Arg215Leu	missense_variant	4/32		NP_001248764.1	O95153B7ZVZ7X5DQQ3A7E2C5
TSPOAP1	NM_024418.3 link	c.571-638G>T		intron_variant			NP_077729.1	O95153-2B7ZVZ7B2RUT8
TSPOAP1-AS1	NR_038410.1 link	n.191C>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9 link	c.644G>T	p.Arg215Leu	missense_variant	4/32	1	NM_004758.4	ENSP00000345824.4		O95153-1

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

495

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

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:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000776

AC:

194

AN:

249904

Hom.:

AF XY:

0.000539

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000307

AC:

448

AN:

1461164

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

193

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00324

AC:

494

AN:

152310

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0111

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.0000915

Hom.:

Bravo

AF:

0.00361

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00103

AC:

125

Asia WGS

AF:

0.00115

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Benign

0.033

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0074

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.065

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.80

Vest4

0.46

MVP

0.26

MPC

0.63

ClinPred

0.044

GERP RS

1.9

Varity_R

0.19

gMVP

0.27

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