dbSNP rs61743284: TSPOAP1:p.Gly79Glu (chr17-58327685-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004758.4(TSPOAP1):c.236G>A(p.Gly79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,613,940 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 32 hom., cov: 32)

Exomes 𝑓: 0.023 ( 476 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.232

Publications

9 publications found

Variant links:

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]

TSPOAP1 links:

TSPOAP1-AS1 (HGNC:44148): (TSPOAP1, SUPT4H1 and RNF43 antisense RNA 1)

TSPOAP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019398034).

BP6

Variant 17-58327685-C-T is Benign according to our data. Variant chr17-58327685-C-T is described in ClinVar as Benign. ClinVar VariationId is 402438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.018 (2745/152348) while in subpopulation SAS AF = 0.0281 (136/4834). AF 95% confidence interval is 0.0243. There are 32 homozygotes in GnomAd4. There are 1365 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSPOAP1	NM_004758.4	MANE Select	c.236G>A	p.Gly79Glu	missense	Exon 1 of 32	NP_004749.2
TSPOAP1	NM_001261835.2		c.236G>A	p.Gly79Glu	missense	Exon 1 of 32	NP_001248764.1
TSPOAP1	NM_024418.3		c.236G>A	p.Gly79Glu	missense	Exon 1 of 31	NP_077729.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSPOAP1	ENST00000343736.9	TSL:1 MANE Select	c.236G>A	p.Gly79Glu	missense	Exon 1 of 32	ENSP00000345824.4
TSPOAP1	ENST00000268893.10	TSL:1	c.236G>A	p.Gly79Glu	missense	Exon 1 of 31	ENSP00000268893.6
TSPOAP1-AS1	ENST00000579527.5	TSL:2	n.280-365C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2748

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00540

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0217

AC:

5452

AN:

251178

AF XY:

0.0232

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0244

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0276

GnomAD4 exome

AF:

0.0231

AC:

33735

AN:

1461592

Hom.:

476

Cov.:

AF XY:

0.0240

AC XY:

17452

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00550

AC:

184

AN:

33478

American (AMR)

AF:

0.0122

AC:

546

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0468

AC:

1224

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0323

AC:

2784

AN:

86258

European-Finnish (FIN)

AF:

0.0233

AC:

1236

AN:

53130

Middle Eastern (MID)

AF:

0.0373

AC:

215

AN:

5768

European-Non Finnish (NFE)

AF:

0.0235

AC:

26098

AN:

1112006

Other (OTH)

AF:

0.0239

AC:

1443

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2253

4506

6758

9011

11264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

972

1944

2916

3888

4860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0180

AC:

2745

AN:

152348

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1365

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00539

AC:

224

AN:

41580

American (AMR)

AF:

0.0171

AC:

262

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0281

AC:

136

AN:

4834

European-Finnish (FIN)

AF:

0.0240

AC:

255

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0237

AC:

1615

AN:

68032

Other (OTH)

AF:

0.0237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

136

273

409

546

682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0170

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0210

AC:

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.0260

AC:

224

ExAC

AF:

0.0217

AC:

2633

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0267

EpiControl

AF:

0.0279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0089

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

0.23

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.75

REVEL

Benign

0.078

Sift

Benign

0.066

Sift4G

Benign

0.33

Polyphen

0.68

Vest4

0.065

MPC

0.27

ClinPred

0.0023

GERP RS

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.085

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over