Variant 17-58310934-G-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 ENST00000343736.9(TSPOAP1):c.3361C>T(p.Pro1121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,564,370 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

TSPOAP1
ENST00000343736.9 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.763

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=0.00540632).

BP6

Variant 17-58310934-G-A is Benign according to our data. Variant chr17-58310934-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPOAP1	NM_004758.4 linkuse as main transcript	c.3361C>T	p.Pro1121Ser	missense_variant	19/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.3361C>T	p.Pro1121Ser	missense_variant	19/32		NP_001248764.1
TSPOAP1	NM_024418.3 linkuse as main transcript	c.3181C>T	p.Pro1061Ser	missense_variant	18/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9 linkuse as main transcript	c.3361C>T	p.Pro1121Ser	missense_variant	19/32	1	NM_004758.4	ENSP00000345824	P2	O95153-1
TSPOAP1	ENST00000268893.10 linkuse as main transcript	c.3181C>T	p.Pro1061Ser	missense_variant	18/31	1		ENSP00000268893	A2	O95153-2
TSPOAP1	ENST00000580669.6 linkuse as main transcript	c.757C>T	p.Pro253Ser	missense_variant	3/16	5		ENSP00000462822

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00127

AC:

258

AN:

203790

Hom.:

AF XY:

0.00129

AC XY:

143

AN XY:

110944

show subpopulations

Gnomad AFR exome

AF:

0.000548

Gnomad AMR exome

AF:

0.00305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000107

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.00171

AC:

2408

AN:

1412054

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1136

AN XY:

699406

show subpopulations

Gnomad4 AFR exome

AF:

0.000225

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.0000439

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000382

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00169

AC:

257

AN:

152316

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00263

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00112

AC:

136

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

.;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0054

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;.;N

REVEL

Benign

0.046

Sift

Benign

0.045

D;.;D

Sift4G

Uncertain

0.044

D;.;T

Polyphen

0.023

B;.;B

Vest4

0.13

MVP

0.30

MPC

0.22

ClinPred

0.0084

GERP RS

3.9

Varity_R

0.042

gMVP

0.27

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