NM_000714.6:c.41C>T

Variant names:

• chr22-43159279-C-T
• rs187866832
• NM_000714.6:c.41C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000714.6(TSPO):​c.41C>T​(p.Ala14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,556,046 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (6 hom.)
• Consequence: TSPO NM_000714.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009313464).
• BP6: Variant 22-43159279-C-T is Benign according to our data. Variant chr22-43159279-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 782174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000714.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPO	NM_000714.6	MANE Select	c.41C>T	p.Ala14Val	missense	Exon 2 of 4	NP_000705.2	P30536-1
	TSPO	NM_001256530.1		c.41C>T	p.Ala14Val	missense	Exon 2 of 4	NP_001243459.1	P30536-1
	TSPO	NM_001256531.1		c.41C>T	p.Ala14Val	missense	Exon 2 of 4	NP_001243460.1	P30536-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPO	ENST00000337554.8	TSL:1 MANE Select	c.41C>T	p.Ala14Val	missense	Exon 2 of 4	ENSP00000338004.3	P30536-1
	TSPO	ENST00000583777.5	TSL:1	c.-130-1773C>T		intron	N/A	ENSP00000463495.1	J3QLD3
	TSPO	ENST00000864336.1		c.41C>T	p.Ala14Val	missense	Exon 2 of 4	ENSP00000534395.1

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 230 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00161 AC: 250 AN: 155014 AF XY: 0.00168

Gnomad AFR exome AF: 0.000477

Gnomad AMR exome AF: 0.000640

Gnomad ASJ exome AF: 0.000121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000336

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00140

GnomAD4 exome AF: 0.00249 AC: 3499 AN: 1403718 Hom.: 6 Cov.: 32 AF XY: 0.00250 AC XY: 1734 AN XY: 693284

African (AFR) AF: 0.000563 AC: 18 AN: 31952

American (AMR) AF: 0.000654 AC: 24 AN: 36672

Ashkenazi Jewish (ASJ) AF: 0.000120 AC: 3 AN: 25048

East Asian (EAS) AF: 0.0000550 AC: 2 AN: 36384

South Asian (SAS) AF: 0.00289 AC: 230 AN: 79454

European-Finnish (FIN) AF: 0.000543 AC: 26 AN: 47868

Middle Eastern (MID) AF: 0.00123 AC: 7 AN: 5694

European-Non Finnish (NFE) AF: 0.00285 AC: 3088 AN: 1082500

Other (OTH) AF: 0.00174 AC: 101 AN: 58146

GnomAD4 genome AF: 0.00152 AC: 231 AN: 152328 Hom.: 0 Cov.: 33 AF XY: 0.00142 AC XY: 106 AN XY: 74488

African (AFR) AF: 0.000673 AC: 28 AN: 41584

American (AMR) AF: 0.00111 AC: 17 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00149

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.000466 AC: 2

ESP6500EA AF: 0.00237 AC: 20

ExAC AF: 0.00112 AC: 128

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.92
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.17
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.076
Sift	Benign	0.33	T
Sift4G	Benign	0.35	T
Polyphen		0.0040	B
Vest4		0.074
MVP		0.048
MPC		0.21
ClinPred		0.0015	T
GERP RS		-2.0
Varity_R		0.029
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs187866832; hg19: chr22-43555285;