Variant rs6972 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.485G>A(p.Arg162His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,587,552 control chromosomes in the GnomAD database, including 47,534 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.19 ( 3338 hom., cov: 34)

Exomes 𝑓: 0.24 ( 44196 hom. )

Consequence

TSPO
NM_000714.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

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:

TSPO (HGNC:):

TSPO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048539937).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 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.485G>A	p.Arg162His	missense_variant	4/4	ENST00000337554.8	NP_000705.2	P30536-1O76068

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPO	ENST00000337554.8 linkuse as main transcript	c.485G>A	p.Arg162His	missense_variant	4/4	1	NM_000714.6	ENSP00000338004.3	P30536-1
TSPO	ENST00000583777.5 linkuse as main transcript	c.173G>A	p.Arg58His	missense_variant	3/3	1		ENSP00000463495.1	J3QLD3
TSPO	ENST00000329563.8 linkuse as main transcript	c.485G>A	p.Arg162His	missense_variant	4/4	3		ENSP00000328973.4	P30536-1
TSPO	ENST00000396265.4 linkuse as main transcript	c.485G>A	p.Arg162His	missense_variant	4/4	5		ENSP00000379563.4	P30536-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29519

AN:

152122

Hom.:

3334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.232

AC:

47924

AN:

206152

Hom.:

5798

AF XY:

0.243

AC XY:

27196

AN XY:

112048

show subpopulations

Gnomad AFR exome

AF:

0.0777

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.246

Gnomad SAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.245

AC:

351214

AN:

1435312

Hom.:

44196

Cov.:

AF XY:

0.248

AC XY:

176529

AN XY:

711958

show subpopulations

Gnomad4 AFR exome

AF:

0.0703

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.194

AC:

29530

AN:

152240

Hom.:

3338

Cov.:

AF XY:

0.195

AC XY:

14532

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.231

Hom.:

6122

Bravo

AF:

0.181

TwinsUK

AF:

0.252

AC:

935

ALSPAC

AF:

0.247

AC:

952

ESP6500AA

AF:

0.0853

AC:

373

ESP6500EA

AF:

0.235

AC:

2008

ExAC

AF:

0.202

AC:

23863

Asia WGS

AF:

0.265

AC:

920

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

T;.;T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.66

.;T;.;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

N;.;N;.

REVEL

Benign

0.026

Sift

Benign

0.22

T;.;T;.

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.019

B;.;B;B

Vest4

0.17

MPC

0.27

ClinPred

0.011

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over