rs6972

Positions:

• chr22-43162966-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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]

ACMG classification

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	UniProt
TSPO	NM_000714.6	c.485G>A	p.Arg162His	missense_variant	4/4	ENST00000337554.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPO	ENST00000337554.8	c.485G>A	p.Arg162His	missense_variant	4/4	1	NM_000714.6	P1
TSPO	ENST00000583777.5	c.173G>A	p.Arg58His	missense_variant	3/3	1
TSPO	ENST00000329563.8	c.485G>A	p.Arg162His	missense_variant	4/4	3		P1
TSPO	ENST00000396265.4	c.485G>A	p.Arg162His	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29519 AN: 152122 Hom.: 3334 Cov.: 34

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

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.: 38 AF XY: 0.248 AC XY: 176529 AN XY: 711958

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.: 34 AF XY: 0.195 AC XY: 14532 AN XY: 74432

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	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
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	N
MetaRNN	Benign	0.0049	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.40	T
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	T
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

Other links and lift over

dbSNP: rs6972; hg19: chr22-43558972; COSMIC: COSV53354339; COSMIC: COSV53354339;