17-58308997-T-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004758.4(TSPOAP1):c.4275A>T(p.Arg1425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,612,302 control chromosomes in the GnomAD database, including 70,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (6642 hom., cov: 33)
  • Exomes 𝑓: 0.29 (63431 hom.)
• Consequence: TSPOAP1 NM_004758.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-58308997-T-A is Benign according to our data. Variant chr17-58308997-T-A is described in ClinVar as [Benign]. Clinvar id is 1294164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.4275A>T	p.Arg1425=	synonymous_variant	22/32	ENST00000343736.9
TSPOAP1	NM_001261835.2	c.4275A>T	p.Arg1425=	synonymous_variant	22/32
TSPOAP1	NM_024418.3	c.4095A>T	p.Arg1365=	synonymous_variant	21/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.4275A>T	p.Arg1425=	synonymous_variant	22/32	1	NM_004758.4	P2
TSPOAP1	ENST00000268893.10	c.4095A>T	p.Arg1365=	synonymous_variant	21/31	1		A2
TSPOAP1	ENST00000580669.6	c.1671A>T	p.Arg557=	synonymous_variant	6/16	5
TSPOAP1	ENST00000582679.1	c.421+970A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44850 AN: 152032 Hom.: 6630 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.320

GnomAD3 exomes AF: 0.282 AC: 69485 AN: 246376 Hom.: 10058 AF XY: 0.283 AC XY: 37946 AN XY: 134270

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.249

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.293 AC: 427995 AN: 1460152 Hom.: 63431 Cov.: 60 AF XY: 0.291 AC XY: 211713 AN XY: 726396

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.295 AC: 44886 AN: 152150 Hom.: 6642 Cov.: 33 AF XY: 0.294 AC XY: 21894 AN XY: 74388

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.318

Alfa AF: 0.301 Hom.: 2264

Bravo AF: 0.292

Asia WGS AF: 0.219 AC: 763 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.309

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.20
Dann	Benign	0.65

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: rs2526360; hg19: chr17-56386358; COSMIC: COSV52108602; COSMIC: COSV52108602;