NM_000714.6:c.71G>C

Variant names:

• chr22-43159309-G-C
• NM_000714.6:c.71G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000714.6(TSPO):​c.71G>C​(p.Arg24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TSPO NM_000714.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105475515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPO	NM_000714.6	c.71G>C	p.Arg24Pro	missense_variant	Exon 2 of 4	ENST00000337554.8	NP_000705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPO	ENST00000337554.8	c.71G>C	p.Arg24Pro	missense_variant	Exon 2 of 4	1	NM_000714.6	ENSP00000338004.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398720 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690180

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T;.;T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.53	.;T;.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N;N;.
REVEL	Benign	0.081
Sift	Benign	0.14	T;T;T;.
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.52	P;.;P;P
Vest4		0.24
MutPred		0.44		Loss of methylation at R24 (P = 0.0067);Loss of methylation at R24 (P = 0.0067);Loss of methylation at R24 (P = 0.0067);Loss of methylation at R24 (P = 0.0067);
MVP		0.19
MPC		0.31
ClinPred		0.20	T
GERP RS		0.69
Varity_R		0.36
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-43555315;