NM_004758.4:c.4942G>A

Variant names:

• chr17-58307652-C-T
• NM_004758.4:c.4942G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004758.4(TSPOAP1):​c.4942G>A​(p.Gly1648Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.70

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40683144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.4942G>A	p.Gly1648Arg	missense_variant	Exon 24 of 32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.4942G>A	p.Gly1648Arg	missense_variant	Exon 24 of 32		NP_001248764.1
TSPOAP1	NM_024418.3	c.4762G>A	p.Gly1588Arg	missense_variant	Exon 23 of 31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.4942G>A	p.Gly1648Arg	missense_variant	Exon 24 of 32	1	NM_004758.4	ENSP00000345824.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 26, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.038	.;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.12	.;.;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Benign	0.23
Sift	Uncertain	0.020	D;.;D
Sift4G	Uncertain	0.0050	D;.;D
Polyphen		1.0	D;.;D
Vest4		0.56
MutPred		0.36		.;.;Gain of solvent accessibility (P = 0.0674);
MVP		0.54
MPC		0.88
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.60

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56385013;