chr6-41043007-T-G

Position:

chr6-41043007-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001010873.3(TSPO2):c.22T>G(p.Phe8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TSPO2
NM_001010873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

TSPO2 (HGNC:21256): (translocator protein 2) Predicted to enable cholesterol binding activity. Involved in amino acid import across plasma membrane. Located in organelle membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TSPO2 links:

OARD1 (HGNC:21257): (O-acyl-ADP-ribose deacylase 1) The protein encoded by this gene is a deacylase that can convert O-acetyl-ADP-ribose to ADP-ribose and acetate, O-propionyl-ADP-ribose to ADP-ribose and propionate, and O-butyryl-ADP-ribose to ADP-ribose and butyrate. The ADP-ribose product is able to inhibit these reactions through a competitive feedback loop. [provided by RefSeq, Jul 2016]

OARD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPO2	NM_001010873.3 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/4	ENST00000373161.6	NP_001010873.1
TSPO2	NM_001159726.1 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/4		NP_001153198.1
TSPO2	XM_011514396.3 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/4		XP_011512698.1
TSPO2	XM_011514397.3 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/4		XP_011512699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPO2	ENST00000373161.6 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/4	1	NM_001010873.3	ENSP00000362255	P1	Q5TGU0-1
TSPO2	ENST00000470917.1 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/4	1		ENSP00000419985	P1	Q5TGU0-1
TSPO2	ENST00000373158.6 linkuse as main transcript	c.22T>G	p.Phe8Val	missense_variant	2/3	1		ENSP00000362252		Q5TGU0-2
OARD1	ENST00000482853.5 linkuse as main transcript	c.*13-7872A>C		intron_variant, NMD_transcript_variant		2		ENSP00000420472

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250998

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Sep 17, 2021

The c.22T>G (p.F8V) alteration is located in exon 2 (coding exon 1) of the TSPO2 gene. This alteration results from a T to G substitution at nucleotide position 22, causing the phenylalanine (F) at amino acid position 8 to be replaced by a valine (V). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;.;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.70

.;T;T

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.0

M;M;M

MutationTaster

Benign

0.83

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.046

D;D;D

Polyphen

0.89

P;.;P

Vest4

0.73

MutPred

0.72

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.48

MPC

1.0

ClinPred

0.94

GERP RS

3.4

Varity_R

0.24

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over