17-58309361-C-T

Position:

• chr17-58309361-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000343736.9(TSPOAP1):​c.3911G>A​(p.Cys1304Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00147 in 1,611,516 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: TSPOAP1 ENST00000343736.9 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.82

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008192748).
• BP6: Variant 17-58309361-C-T is Benign according to our data. Variant chr17-58309361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.3911G>A	p.Cys1304Tyr	missense_variant	22/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.3911G>A	p.Cys1304Tyr	missense_variant	22/32		NP_001248764.1
TSPOAP1	NM_024418.3	c.3731G>A	p.Cys1244Tyr	missense_variant	21/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.3911G>A	p.Cys1304Tyr	missense_variant	22/32	1	NM_004758.4	ENSP00000345824	P2
TSPOAP1	ENST00000268893.10	c.3731G>A	p.Cys1244Tyr	missense_variant	21/31	1		ENSP00000268893	A2
TSPOAP1	ENST00000580669.6	c.1307G>A	p.Cys436Tyr	missense_variant	6/16	5		ENSP00000462822
TSPOAP1	ENST00000582679.1	c.421+606G>A		intron_variant		5		ENSP00000462710

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000958 AC: 234 AN: 244318 Hom.: 0 AF XY: 0.000972 AC XY: 129 AN XY: 132758

Gnomad AFR exome AF: 0.000314

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000230

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00183

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.00149 AC: 2176 AN: 1459268 Hom.: 3 Cov.: 34 AF XY: 0.00146 AC XY: 1062 AN XY: 725874

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.0000767

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.0000387

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.00118 AC XY: 88 AN XY: 74440

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00167 Hom.: 1

Bravo AF: 0.00125

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.00103 AC: 125

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.080	.;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.0082	T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.5	.;.;M
MutationTaster	Benign	0.86	N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.5	D;.;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	D;.;D
Sift4G	Uncertain	0.057	T;.;T
Polyphen		0.63	P;.;B
Vest4		0.52
MVP		0.73
MPC		0.57
ClinPred		0.079	T
GERP RS		3.4
Varity_R		0.46
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs142234067; hg19: chr17-56386722;