NM_004758.4:c.4700C>G

Variant names:

• chr17-58308572-G-C
• rs143530655
• NM_004758.4:c.4700C>G

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.4700C>G​(p.Ala1567Gly) 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. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A1567V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• 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=0.09774563).

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.4700C>G	p.Ala1567Gly	missense	Exon 22 of 32	NP_004749.2	O95153-1
	TSPOAP1	NM_001261835.2		c.4700C>G	p.Ala1567Gly	missense	Exon 22 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.4520C>G	p.Ala1507Gly	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.4700C>G	p.Ala1567Gly	missense	Exon 22 of 32	ENSP00000345824.4	O95153-1
	TSPOAP1	ENST00000268893.10	TSL:1	c.4520C>G	p.Ala1507Gly	missense	Exon 21 of 31	ENSP00000268893.6	O95153-2
	TSPOAP1	ENST00000580669.6	TSL:5	c.2096C>G	p.Ala699Gly	missense	Exon 6 of 16	ENSP00000462822.2	J3KT64

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.38
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.073
Sift	Benign	0.064	T
Sift4G	Benign	0.36	T
Polyphen		0.010	B
Vest4		0.19
MutPred		0.20		Gain of glycosylation at S1566 (P = 0.047)
MVP		0.21
MPC		0.40
ClinPred		0.31	T
GERP RS		4.2
Varity_R		0.097
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs143530655; hg19: chr17-56385933;