NM_000714.6:c.161G>T

Variant names:

• chr22-43159399-G-T
• NM_000714.6:c.161G>T

Variant summary

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

The NM_000714.6(TSPO):​c.161G>T​(p.Gly54Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000724 in 1,381,210 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TSPO NM_000714.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPO	NM_000714.6	c.161G>T	p.Gly54Val	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.161G>T	p.Gly54Val	missense_variant	Exon 2 of 4	1	NM_000714.6	ENSP00000338004.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381210 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 680938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000284

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	0.14
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.;T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	.;D;.;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.35	N;N;N;.
REVEL	Benign	0.10
Sift	Benign	0.18	T;T;T;.
Sift4G	Benign	0.099	T;T;T;T
Polyphen		0.82	P;.;P;P
Vest4		0.59
MutPred		0.64		Gain of catalytic residue at G54 (P = 0.1401);Gain of catalytic residue at G54 (P = 0.1401);Gain of catalytic residue at G54 (P = 0.1401);Gain of catalytic residue at G54 (P = 0.1401);
MVP		0.54
MPC		0.66
ClinPred		0.88	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.59

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: chr22-43555405;