Variant rs6971 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000714.6(TSPO):c.439A>G(p.Thr147Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,593,126 control chromosomes in the GnomAD database, including 408,706 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.75 ( 43147 hom., cov: 35)

Exomes 𝑓: 0.71 ( 365559 hom. )

Consequence

TSPO
NM_000714.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.42

Variant links:

Genes affected

TSPO (HGNC:1158): (translocator protein) Present mainly in the mitochondrial compartment of peripheral tissues, the protein encoded by this gene interacts with some benzodiazepines and has different affinities than its endogenous counterpart. The protein is a key factor in the flow of cholesterol into mitochondria to permit the initiation of steroid hormone synthesis. Alternatively spliced transcript variants have been reported; one of the variants lacks an internal exon and is considered non-coding, and the other variants encode the same protein. [provided by RefSeq, Feb 2012]

TSPO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0709306E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPO	NM_000714.6 linkuse as main transcript	c.439A>G	p.Thr147Ala	missense_variant	4/4	ENST00000337554.8	NP_000705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPO	ENST00000337554.8 linkuse as main transcript	c.439A>G	p.Thr147Ala	missense_variant	4/4	1	NM_000714.6	ENSP00000338004	P1	P30536-1
TSPO	ENST00000583777.5 linkuse as main transcript	c.127A>G	p.Thr43Ala	missense_variant	3/3	1		ENSP00000463495
TSPO	ENST00000329563.8 linkuse as main transcript	c.439A>G	p.Thr147Ala	missense_variant	4/4	3		ENSP00000328973	P1	P30536-1
TSPO	ENST00000396265.4 linkuse as main transcript	c.439A>G	p.Thr147Ala	missense_variant	4/4	5		ENSP00000379563	P1	P30536-1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113905

AN:

152134

Hom.:

43087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.806

Gnomad ASJ

AF:

0.705

Gnomad EAS

AF:

0.969

Gnomad SAS

AF:

0.848

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.759

GnomAD3 exomes

AF:

0.758

AC:

164158

AN:

216438

Hom.:

63350

AF XY:

0.755

AC XY:

88465

AN XY:

117106

show subpopulations

Gnomad AFR exome

AF:

0.803

Gnomad AMR exome

AF:

0.863

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.977

Gnomad SAS exome

AF:

0.842

Gnomad FIN exome

AF:

0.672

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.734

GnomAD4 exome

AF:

0.709

AC:

1020986

AN:

1440874

Hom.:

365559

Cov.:

AF XY:

0.712

AC XY:

509157

AN XY:

714894

show subpopulations

Gnomad4 AFR exome

AF:

0.811

Gnomad4 AMR exome

AF:

0.855

Gnomad4 ASJ exome

AF:

0.700

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.842

Gnomad4 FIN exome

AF:

0.682

Gnomad4 NFE exome

AF:

0.681

Gnomad4 OTH exome

AF:

0.728

GnomAD4 genome

AF:

0.749

AC:

114025

AN:

152252

Hom.:

43147

Cov.:

AF XY:

0.752

AC XY:

55990

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.813

Gnomad4 AMR

AF:

0.807

Gnomad4 ASJ

AF:

0.705

Gnomad4 EAS

AF:

0.969

Gnomad4 SAS

AF:

0.847

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.704

Hom.:

54604

Bravo

AF:

0.762

TwinsUK

AF:

0.672

AC:

2492

ALSPAC

AF:

0.687

AC:

2649

ESP6500AA

AF:

0.802

AC:

3526

ESP6500EA

AF:

0.687

AC:

5905

ExAC

AF:

0.738

AC:

88110

Asia WGS

AF:

0.890

AC:

3095

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.036

T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.30

.;T;.;T

MetaRNN

Benign

0.0000011

T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

3.7

N;.;N;.

REVEL

Benign

0.16

Sift

Benign

1.0

T;.;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.14

MPC

0.21

ClinPred

0.021

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.60

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over