Genetic Variant TSPO:p.Arg162Leu (chr22-43162966-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000714.6(TSPO):c.485G>T(p.Arg162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TSPO
NM_000714.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14243135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPO	NM_000714.6 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 4 of 4	ENST00000337554.8	NP_000705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TSPO	ENST00000337554.8 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 4 of 4	1	NM_000714.6	ENSP00000338004.3
TSPO	ENST00000583777.5 link	c.173G>T	p.Arg58Leu	missense_variant	Exon 3 of 3	1		ENSP00000463495.1
TSPO	ENST00000329563.8 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 4 of 4	3		ENSP00000328973.4
TSPO	ENST00000396265.4 link	c.485G>T	p.Arg162Leu	missense_variant	Exon 4 of 4	5		ENSP00000379563.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32952

American (AMR)

AF:

0.00

AC:

AN:

41178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25722

East Asian (EAS)

AF:

0.00

AC:

AN:

37976

South Asian (SAS)

AF:

0.00

AC:

AN:

83004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1099922

Other (OTH)

AF:

0.00

AC:

AN:

59284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.;T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.75

.;T;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

N;.;N;.

REVEL

Benign

0.050

Sift

Uncertain

0.012

D;.;D;.

Sift4G

Uncertain

0.028

D;D;D;D

Polyphen

0.54

P;.;P;P

Vest4

0.31

MutPred

0.40

Loss of MoRF binding (P = 3e-04);.;Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);

MVP

0.21

MPC

0.35

ClinPred

0.42

GERP RS

3.3

Varity_R

0.19

gMVP

0.71

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over