Variant 17-58308636-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004758.4(TSPOAP1):c.4636C>T(p.Pro1546Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,608,672 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 43 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 36 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.219

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015099049).

BP6

Variant 17-58308636-G-A is Benign according to our data. Variant chr17-58308636-G-A is described in ClinVar as [Benign]. Clinvar id is 768901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2145/152342) while in subpopulation AFR AF= 0.0482 (2002/41572). AF 95% confidence interval is 0.0464. There are 43 homozygotes in gnomad4. There are 982 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TSPOAP1	NM_004758.4 linkuse as main transcript	c.4636C>T	p.Pro1546Ser	missense_variant	22/32	ENST00000343736.9
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.4636C>T	p.Pro1546Ser	missense_variant	22/32
TSPOAP1	NM_024418.3 linkuse as main transcript	c.4456C>T	p.Pro1486Ser	missense_variant	21/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9 linkuse as main transcript	c.4636C>T	p.Pro1546Ser	missense_variant	22/32	1	NM_004758.4	P2	O95153-1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2141

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00380

AC:

944

AN:

248340

Hom.:

AF XY:

0.00285

AC XY:

384

AN XY:

134704

show subpopulations

Gnomad AFR exome

AF:

0.0495

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000882

Gnomad NFE exome

AF:

0.000385

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00154

AC:

2236

AN:

1456330

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

996

AN XY:

723610

show subpopulations

Gnomad4 AFR exome

AF:

0.0458

Gnomad4 AMR exome

AF:

0.00261

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.000630

Gnomad4 NFE exome

AF:

0.000282

Gnomad4 OTH exome

AF:

0.00355

GnomAD4 genome

AF:

0.0141

AC:

2145

AN:

152342

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

982

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0482

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00410

Hom.:

Bravo

AF:

0.0153

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0457

AC:

201

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00453

AC:

550

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

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	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.020

.;.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.070

Sift

Benign

0.16

T;.;T

Sift4G

Benign

0.73

T;.;T

Polyphen

0.034

B;.;B

Vest4

0.15

MVP

0.26

MPC

0.22

ClinPred

0.0067

GERP RS

3.2

Varity_R

0.053

gMVP

0.52

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