17-58308636-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004758.4(TSPOAP1):c.4636C>T(p.Pro1546Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,608,672 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (36 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.219

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015099049).
• BP6: Variant 17-58308636-G-A is Benign according to our data. Variant chr17-58308636-G-A is described in ClinVar as [Benign]. Clinvar id is 768901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2145/152342) while in subpopulation AFR AF= 0.0482 (2002/41572). AF 95% confidence interval is 0.0464. There are 43 homozygotes in gnomad4. There are 982 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.4636C>T	p.Pro1546Ser	missense_variant	22/32	ENST00000343736.9
TSPOAP1	NM_001261835.2	c.4636C>T	p.Pro1546Ser	missense_variant	22/32
TSPOAP1	NM_024418.3	c.4456C>T	p.Pro1486Ser	missense_variant	21/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.4636C>T	p.Pro1546Ser	missense_variant	22/32	1	NM_004758.4	P2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2141 AN: 152224 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00380 AC: 944 AN: 248340 Hom.: 18 AF XY: 0.00285 AC XY: 384 AN XY: 134704

Gnomad AFR exome AF: 0.0495

Gnomad AMR exome AF: 0.00224

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000882

Gnomad NFE exome AF: 0.000385

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00154 AC: 2236 AN: 1456330 Hom.: 36 Cov.: 31 AF XY: 0.00138 AC XY: 996 AN XY: 723610

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.00261

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.000630

Gnomad4 NFE exome AF: 0.000282

Gnomad4 OTH exome AF: 0.00355

GnomAD4 genome AF: 0.0141 AC: 2145 AN: 152342 Hom.: 43 Cov.: 33 AF XY: 0.0132 AC XY: 982 AN XY: 74506

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00410 Hom.: 14

Bravo AF: 0.0153

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0457 AC: 201

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00453 AC: 550

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	16
Dann	Benign	0.94
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.77	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N;.;N
REVEL	Benign	0.070
Sift	Benign	0.16	T;.;T
Sift4G	Benign	0.73	T;.;T
Polyphen		0.034	B;.;B
Vest4		0.15
MVP		0.26
MPC		0.22
ClinPred		0.0067	T
GERP RS		3.2
Varity_R		0.053
gMVP		0.52

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: rs61732758; hg19: chr17-56385997;