17-58305843-C-T

Variant names:

• chr17-58305843-C-T
• rs148464443
• NM_004758.4:c.5247G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004758.4(TSPOAP1):​c.5247G>A​(p.Gln1749Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,612,946 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (6 hom.)
• Consequence: TSPOAP1 NM_004758.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.268
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-58305843-C-T is Benign according to our data. Variant chr17-58305843-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.268 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	NM_004758.4	MANE Select	c.5247G>A	p.Gln1749Gln	synonymous	Exon 27 of 32	NP_004749.2	O95153-1
	TSPOAP1	NM_001261835.2		c.5220G>A	p.Gln1740Gln	synonymous	Exon 27 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.5067G>A	p.Gln1689Gln	synonymous	Exon 26 of 31	NP_077729.1	O95153-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	ENST00000343736.9	TSL:1 MANE Select	c.5247G>A	p.Gln1749Gln	synonymous	Exon 27 of 32	ENSP00000345824.4	O95153-1
	TSPOAP1	ENST00000268893.10	TSL:1	c.5067G>A	p.Gln1689Gln	synonymous	Exon 26 of 31	ENSP00000268893.6	O95153-2
	TSPOAP1	ENST00000581675.5	TSL:1	c.39G>A	p.Gln13Gln	synonymous	Exon 2 of 6	ENSP00000462518.1	A0A0C4DGN5

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152172 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000870 AC: 217 AN: 249544 AF XY: 0.00115

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000800

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000451 AC: 659 AN: 1460656 Hom.: 6 Cov.: 33 AF XY: 0.000651 AC XY: 473 AN XY: 726702

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.000112 AC: 5 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00581 AC: 501 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52650

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5760

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111710

Other (OTH) AF: 0.000630 AC: 38 AN: 60354

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152290 Hom.: 2 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000204 Hom.: 0

Bravo AF: 0.000110

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.5
DANN	Benign	0.60
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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: rs148464443; hg19: chr17-56383204;