17-58309371-C-T

Position:

chr17-58309371-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004758.4(TSPOAP1):c.3901G>A(p.Asp1301Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,608,002 control chromosomes in the GnomAD database, including 541 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 0.018 ( 33 hom., cov: 32)

Exomes 𝑓: 0.024 ( 508 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002943635).

BP6

Variant 17-58309371-C-T is Benign according to our data. Variant chr17-58309371-C-T is described in ClinVar as [Benign]. Clinvar id is 402437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58309371-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0183 (2777/152156) while in subpopulation SAS AF= 0.0305 (147/4816). AF 95% confidence interval is 0.0265. There are 33 homozygotes in gnomad4. There are 1376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPOAP1	NM_004758.4 linkuse as main transcript	c.3901G>A	p.Asp1301Asn	missense_variant	22/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.3901G>A	p.Asp1301Asn	missense_variant	22/32		NP_001248764.1
TSPOAP1	NM_024418.3 linkuse as main transcript	c.3721G>A	p.Asp1241Asn	missense_variant	21/31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9 linkuse as main transcript	c.3901G>A	p.Asp1301Asn	missense_variant	22/32	1	NM_004758.4	ENSP00000345824	P2	O95153-1
TSPOAP1	ENST00000268893.10 linkuse as main transcript	c.3721G>A	p.Asp1241Asn	missense_variant	21/31	1		ENSP00000268893	A2	O95153-2
TSPOAP1	ENST00000580669.6 linkuse as main transcript	c.1297G>A	p.Asp433Asn	missense_variant	6/16	5		ENSP00000462822
TSPOAP1	ENST00000582679.1 linkuse as main transcript	c.421+596G>A		intron_variant		5		ENSP00000462710

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2779

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00394

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0307

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0226

AC:

5462

AN:

241648

Hom.:

AF XY:

0.0243

AC XY:

3196

AN XY:

131454

show subpopulations

Gnomad AFR exome

AF:

0.00387

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0530

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.0249

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0236

AC:

34343

AN:

1455846

Hom.:

508

Cov.:

AF XY:

0.0246

AC XY:

17827

AN XY:

723784

show subpopulations

Gnomad4 AFR exome

AF:

0.00392

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.0521

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0355

Gnomad4 FIN exome

AF:

0.0233

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0183

AC:

2777

AN:

152156

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1376

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00393

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.0545

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0305

Gnomad4 FIN

AF:

0.0239

Gnomad4 NFE

AF:

0.0245

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0245

Hom.:

Bravo

AF:

0.0170

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00568

AC:

ESP6500EA

AF:

0.0259

AC:

223

ExAC

AF:

0.0224

AC:

2715

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0280

EpiControl

AF:

0.0292

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

.;.;T

Eigen

Benign

0.053

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.5

.;.;M

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.22

Sift

Uncertain

0.018

D;.;D

Sift4G

Uncertain

0.045

D;.;D

Polyphen

0.014

B;.;B

Vest4

0.28

MPC

0.21

ClinPred

0.011

GERP RS

5.6

Varity_R

0.13

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over