17-58305692-C-T

Variant summary

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

The NM_004758.4(TSPOAP1):c.5258-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,364,492 control chromosomes in the GnomAD database, including 3,487 homozygotes. 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: 𝑓 0.070 (365 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3122 hom.)
• Consequence: TSPOAP1 NM_004758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

Genes affected

TSPOAP1 (HGNC:16831): (TSPO associated protein 1) Enables benzodiazepine receptor binding activity. Predicted to be involved in regulation of presynaptic cytosolic calcium ion concentration. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.5258-49G>A		intron_variant		ENST00000343736.9
TSPOAP1	NM_001261835.2	c.5231-49G>A		intron_variant
TSPOAP1	NM_024418.3	c.5078-49G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.5258-49G>A		intron_variant		1	NM_004758.4	P2

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10597 AN: 152040 Hom.: 362 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0810

GnomAD3 exomes AF: 0.0725 AC: 12447 AN: 171644 Hom.: 510 AF XY: 0.0743 AC XY: 6774 AN XY: 91164

Gnomad AFR exome AF: 0.0670

Gnomad AMR exome AF: 0.0452

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0963

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.0683

Gnomad NFE exome AF: 0.0673

Gnomad OTH exome AF: 0.0739

GnomAD4 exome AF: 0.0680 AC: 82443 AN: 1212334 Hom.: 3122 Cov.: 17 AF XY: 0.0697 AC XY: 42124 AN XY: 604086

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.0481

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0789

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0702

Gnomad4 NFE exome AF: 0.0640

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0698 AC: 10628 AN: 152158 Hom.: 365 Cov.: 32 AF XY: 0.0715 AC XY: 5316 AN XY: 74388

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0802

Alfa AF: 0.0638 Hom.: 245

Bravo AF: 0.0690

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.35
Dann	Benign	0.29

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: rs3744103; hg19: chr17-56383053;