17-58305692-C-T

Variant names:

• chr17-58305692-C-T
• rs3744103
• NM_004758.4:c.5258-49G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TSPOAP1 Gene-Disease associations (from GenCC):

• TH-deficient dopa-responsive dystonia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.5258-49G>A		intron_variant	Intron 27 of 31	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.5231-49G>A		intron_variant	Intron 27 of 31		NP_001248764.1
TSPOAP1	NM_024418.3	c.5078-49G>A		intron_variant	Intron 26 of 30		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.5258-49G>A		intron_variant	Intron 27 of 31	1	NM_004758.4	ENSP00000345824.4

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

GnomAD2 exomes AF: 0.0725 AC: 12447 AN: 171644 AF XY: 0.0743

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 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

African (AFR) AF: 0.0671 AC: 1948 AN: 29036

American (AMR) AF: 0.0481 AC: 1760 AN: 36576

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2492 AN: 20892

East Asian (EAS) AF: 0.0789 AC: 2989 AN: 37900

South Asian (SAS) AF: 0.103 AC: 7444 AN: 72030

European-Finnish (FIN) AF: 0.0702 AC: 3359 AN: 47826

Middle Eastern (MID) AF: 0.0703 AC: 354 AN: 5036

European-Non Finnish (NFE) AF: 0.0640 AC: 58358 AN: 911286

Other (OTH) AF: 0.0722 AC: 3739 AN: 51752

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

African (AFR) AF: 0.0644 AC: 2672 AN: 41508

American (AMR) AF: 0.0643 AC: 984 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3464

East Asian (EAS) AF: 0.0906 AC: 468 AN: 5168

South Asian (SAS) AF: 0.101 AC: 490 AN: 4832

European-Finnish (FIN) AF: 0.0745 AC: 791 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4572 AN: 67964

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0673 Hom.: 393

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
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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: rs3744103; hg19: chr17-56383053;