Variant 22-43159279-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000714.6(TSPO):c.41C>T(p.Ala14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,556,046 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 6 hom. )

Consequence

TSPO
NM_000714.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.166

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009313464).

BP6

Variant 22-43159279-C-T is Benign according to our data. Variant chr22-43159279-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782174.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPO	NM_000714.6 linkuse as main transcript	c.41C>T	p.Ala14Val	missense_variant	2/4	ENST00000337554.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPO	ENST00000337554.8 linkuse as main transcript	c.41C>T	p.Ala14Val	missense_variant	2/4	1	NM_000714.6	P1	P30536-1

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

230

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00161

AC:

250

AN:

155014

Hom.:

AF XY:

0.00168

AC XY:

140

AN XY:

83254

show subpopulations

Gnomad AFR exome

AF:

0.000477

Gnomad AMR exome

AF:

0.000640

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00267

Gnomad FIN exome

AF:

0.000336

Gnomad NFE exome

AF:

0.00264

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.00249

AC:

3499

AN:

1403718

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

1734

AN XY:

693284

show subpopulations

Gnomad4 AFR exome

AF:

0.000563

Gnomad4 AMR exome

AF:

0.000654

Gnomad4 ASJ exome

AF:

0.000120

Gnomad4 EAS exome

AF:

0.0000550

Gnomad4 SAS exome

AF:

0.00289

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00152

AC:

231

AN:

152328

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00149

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000466

AC:

ESP6500EA

AF:

0.00237

AC:

ExAC

AF:

0.00112

AC:

128

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

DANN

Benign

0.92

DEOGEN2

Benign

0.0031

T;.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.61

.;T;.;T

MetaRNN

Benign

0.0093

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

1.4

N;N;N;.

REVEL

Benign

0.076

Sift

Benign

0.33

T;T;T;.

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.0040

B;.;B;B

Vest4

0.074

MVP

0.048

MPC

0.21

ClinPred

0.0015

GERP RS

-2.0

Varity_R

0.029

gMVP

0.11

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