17-58309106-G-C

Position:

• chr17-58309106-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004758.4(TSPOAP1):​c.4166C>G​(p.Ala1389Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.511

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05538827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.4166C>G	p.Ala1389Gly	missense_variant	22/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.4166C>G	p.Ala1389Gly	missense_variant	22/32		NP_001248764.1
TSPOAP1	NM_024418.3	c.3986C>G	p.Ala1329Gly	missense_variant	21/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.4166C>G	p.Ala1389Gly	missense_variant	22/32	1	NM_004758.4	ENSP00000345824.4
TSPOAP1	ENST00000268893.10	c.3986C>G	p.Ala1329Gly	missense_variant	21/31	1		ENSP00000268893.6
TSPOAP1	ENST00000580669.6	c.1562C>G	p.Ala521Gly	missense_variant	6/16	5		ENSP00000462822.2
TSPOAP1	ENST00000582679.1	c.420+861C>G		intron_variant		5		ENSP00000462710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

TSPOAP1: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0061	.;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	.;.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.22	N;.;N
REVEL	Benign	0.038
Sift	Benign	0.40	T;.;T
Sift4G	Benign	0.47	T;.;T
Polyphen		0.0060	B;.;B
Vest4		0.088
MutPred		0.11		.;.;Gain of relative solvent accessibility (P = 0.0166);
MVP		0.10
MPC		0.21
ClinPred		0.035	T
GERP RS		1.7
Varity_R		0.035
gMVP		0.34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56386467;