17-58308656-G-A

Variant names:

• chr17-58308656-G-A
• rs140503332
• NM_004758.4:c.4616C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004758.4(TSPOAP1):​c.4616C>T​(p.Pro1539Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000145 in 1,609,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.095044255).

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.4616C>T	p.Pro1539Leu	missense	Exon 22 of 32	NP_004749.2	O95153-1
	TSPOAP1	NM_001261835.2		c.4616C>T	p.Pro1539Leu	missense	Exon 22 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.4436C>T	p.Pro1479Leu	missense	Exon 21 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.4616C>T	p.Pro1539Leu	missense	Exon 22 of 32	ENSP00000345824.4	O95153-1
	TSPOAP1	ENST00000268893.10	TSL:1	c.4436C>T	p.Pro1479Leu	missense	Exon 21 of 31	ENSP00000268893.6	O95153-2
	TSPOAP1	ENST00000580669.6	TSL:5	c.2012C>T	p.Pro671Leu	missense	Exon 6 of 16	ENSP00000462822.2	J3KT64

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152238 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000645 AC: 16 AN: 247900 AF XY: 0.0000817

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: 0.000144

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000150 AC: 219 AN: 1457702 Hom.: 0 Cov.: 31 AF XY: 0.000138 AC XY: 100 AN XY: 724588

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.000187 AC: 208 AN: 1109642

Other (OTH) AF: 0.000183 AC: 11 AN: 60218

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152238 Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000170

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000491

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.056	T
Polyphen		0.20	B
Vest4		0.27
MVP		0.21
MPC		0.25
ClinPred		0.16	T
GERP RS		5.3
Varity_R		0.083
gMVP		0.41
Mutation Taster		=91/9	polymorphism

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: rs140503332; hg19: chr17-56386017;