17-58310741-C-A

Position:

• chr17-58310741-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000343736.9(TSPOAP1):​c.3470G>T​(p.Gly1157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,612,064 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (204 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (203 hom.)
• Consequence: TSPOAP1 ENST00000343736.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.858

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019123852).
• BP6: Variant 17-58310741-C-A is Benign according to our data. Variant chr17-58310741-C-A is described in ClinVar as [Benign]. Clinvar id is 781373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.3470G>T	p.Gly1157Val	missense_variant	20/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.3470G>T	p.Gly1157Val	missense_variant	20/32		NP_001248764.1
TSPOAP1	NM_024418.3	c.3290G>T	p.Gly1097Val	missense_variant	19/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.3470G>T	p.Gly1157Val	missense_variant	20/32	1	NM_004758.4	ENSP00000345824	P2
TSPOAP1	ENST00000268893.10	c.3290G>T	p.Gly1097Val	missense_variant	19/31	1		ENSP00000268893	A2
TSPOAP1	ENST00000580669.6	c.866G>T	p.Gly289Val	missense_variant	4/16	5		ENSP00000462822
TSPOAP1	ENST00000582679.1			upstream_gene_variant		5		ENSP00000462710

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4336 AN: 152174 Hom.: 202 Cov.: 33

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0181

GnomAD3 exomes AF: 0.00697 AC: 1714 AN: 245838 Hom.: 71 AF XY: 0.00512 AC XY: 686 AN XY: 133916

Gnomad AFR exome AF: 0.0981

Gnomad AMR exome AF: 0.00490

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00287 AC: 4196 AN: 1459772 Hom.: 203 Cov.: 32 AF XY: 0.00241 AC XY: 1748 AN XY: 726028

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.00555

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000603

Gnomad4 OTH exome AF: 0.00655

GnomAD4 genome AF: 0.0286 AC: 4350 AN: 152292 Hom.: 204 Cov.: 33 AF XY: 0.0271 AC XY: 2019 AN XY: 74474

Gnomad4 AFR AF: 0.0998

Gnomad4 AMR AF: 0.00954

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00892 Hom.: 38

Bravo AF: 0.0322

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0806 AC: 354

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00863 AC: 1046

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.086	.;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.72	T;T;T
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;.;M
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N;.;N
REVEL	Benign	0.058
Sift	Uncertain	0.0090	D;.;D
Sift4G	Benign	0.27	T;.;T
Polyphen		0.74	P;.;B
Vest4		0.28
MVP		0.16
MPC		0.26
ClinPred		0.018	T
GERP RS		4.6
Varity_R		0.21
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs112573747; hg19: chr17-56388102;