TSPOAP1 p.Gly1582Arg

Variant names:

• chr17-58307929-C-G
• NM_004758.4:c.4744G>C
• TSPOAP1 p.Gly1582Arg

Your query was ambiguous. Multiple possible variants found:

• chr17-58307929-C-G
• chr17-58307929-C-T
• chr17-58307927-TCC-ACG
• chr17-58307927-TCC-GCG
• chr17-58307927-TCC-CCG
• chr17-58307927-TCC-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004758.4(TSPOAP1):​c.4744G>C​(p.Gly1582Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07558465).

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.4744G>C	p.Gly1582Arg	missense	Exon 23 of 32	NP_004749.2	O95153-1
	TSPOAP1	NM_001261835.2		c.4744G>C	p.Gly1582Arg	missense	Exon 23 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.4564G>C	p.Gly1522Arg	missense	Exon 22 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.4744G>C	p.Gly1582Arg	missense	Exon 23 of 32	ENSP00000345824.4	O95153-1
	TSPOAP1	ENST00000268893.10	TSL:1	c.4564G>C	p.Gly1522Arg	missense	Exon 22 of 31	ENSP00000268893.6	O95153-2
	TSPOAP1	ENST00000580669.6	TSL:5	c.2140G>C	p.Gly714Arg	missense	Exon 7 of 16	ENSP00000462822.2	J3KT64

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.35
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.24	T
Sift4G	Benign	0.26	T
Varity_R		0.053
gMVP		0.39

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-56385290;