chr17-58305692-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004758.4(TSPOAP1):​c.5258-49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000742 in 1,213,096 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: 32)
  • Exomes 𝑓: 0.0000074 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	NM_004758.4	MANE Select	c.5258-49G>T		intron	N/A	NP_004749.2
	TSPOAP1	NM_001261835.2		c.5231-49G>T		intron	N/A	NP_001248764.1
	TSPOAP1	NM_024418.3		c.5078-49G>T		intron	N/A	NP_077729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	ENST00000343736.9	TSL:1 MANE Select	c.5258-49G>T		intron	N/A	ENSP00000345824.4
	TSPOAP1	ENST00000268893.10	TSL:1	c.5078-49G>T		intron	N/A	ENSP00000268893.6
	TSPOAP1	ENST00000581675.5	TSL:1	c.50-49G>T		intron	N/A	ENSP00000462518.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000583 AC: 1 AN: 171644 AF XY: 0.0000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000742 AC: 9 AN: 1213096 Hom.: 0 Cov.: 17 AF XY: 0.00000993 AC XY: 6 AN XY: 604470

African (AFR) AF: 0.00 AC: 0 AN: 29056

American (AMR) AF: 0.00 AC: 0 AN: 36596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20908

East Asian (EAS) AF: 0.00 AC: 0 AN: 37914

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 72082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5038

European-Non Finnish (NFE) AF: 0.00000877 AC: 8 AN: 911874

Other (OTH) AF: 0.00 AC: 0 AN: 51786

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-0.86

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;