22-43160916-C-A

Variant names:

• chr22-43160916-C-A
• rs113515
• NM_000714.6:c.183-136C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000714.6(TSPO):​c.183-136C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 916,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000011 (0 hom.)
• Consequence: TSPO NM_000714.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPO	NM_000714.6	c.183-136C>A		intron_variant	Intron 2 of 3	ENST00000337554.8	NP_000705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPO	ENST00000337554.8	c.183-136C>A		intron_variant	Intron 2 of 3	1	NM_000714.6	ENSP00000338004.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 916698 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 457008

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21012

American (AMR) AF: 0.00 AC: 0 AN: 17768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15950

East Asian (EAS) AF: 0.00 AC: 0 AN: 32746

South Asian (SAS) AF: 0.00 AC: 0 AN: 51848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2998

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 693326

Other (OTH) AF: 0.0000247 AC: 1 AN: 40498

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113515; hg19: chr22-43556922;