Variant 17-58310891-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004758.4(TSPOAP1):c.3404C>T(p.Pro1135Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000669 in 1,542,068 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 2 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.334

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019965917).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPOAP1	NM_004758.4 linkuse as main transcript	c.3404C>T	p.Pro1135Leu	missense_variant	19/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.3404C>T	p.Pro1135Leu	missense_variant	19/32		NP_001248764.1
TSPOAP1	NM_024418.3 linkuse as main transcript	c.3224C>T	p.Pro1075Leu	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.3404C>T	p.Pro1135Leu	missense_variant	19/32	1	NM_004758.4	ENSP00000345824	P2	O95153-1
TSPOAP1	ENST00000268893.10 linkuse as main transcript	c.3224C>T	p.Pro1075Leu	missense_variant	18/31	1		ENSP00000268893	A2	O95153-2
TSPOAP1	ENST00000580669.6 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant	3/16	5		ENSP00000462822

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000764

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000262

AC:

AN:

186836

Hom.:

AF XY:

0.000278

AC XY:

AN XY:

100684

show subpopulations

Gnomad AFR exome

AF:

0.0000701

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000534

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000700

AC:

973

AN:

1389854

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

472

AN XY:

685428

show subpopulations

Gnomad4 AFR exome

AF:

0.000130

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000865

Gnomad4 OTH exome

AF:

0.000595

GnomAD4 genome

AF:

0.000381

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000475

Hom.:

Bravo

AF:

0.000397

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000824

AC:

ExAC

AF:

0.000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.3404C>T (p.P1135L) alteration is located in exon 19 (coding exon 19) of the TSPOAP1 gene. This alteration results from a C to T substitution at nucleotide position 3404, causing the proline (P) at amino acid position 1135 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.4

DANN

Benign

0.76

DEOGEN2

Benign

0.0080

.;.;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.48

N;.;N

REVEL

Benign

0.021

Sift

Benign

0.67

T;.;T

Sift4G

Benign

0.64

T;.;T

Polyphen

0.0050

B;.;B

Vest4

0.050

MVP

0.076

MPC

0.22

ClinPred

0.0079

GERP RS

-0.27

Varity_R

0.028

gMVP

0.17

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