Variant chr17-58308621-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004758.4(TSPOAP1):c.4651C>T(p.Arg1551Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,448,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0680

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14529562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSPOAP1	NM_004758.4 linkuse as main transcript	c.4651C>T	p.Arg1551Cys	missense_variant	22/32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2 linkuse as main transcript	c.4651C>T	p.Arg1551Cys	missense_variant	22/32		NP_001248764.1
TSPOAP1	NM_024418.3 linkuse as main transcript	c.4471C>T	p.Arg1491Cys	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.4651C>T	p.Arg1551Cys	missense_variant	22/32	1	NM_004758.4	ENSP00000345824	P2	O95153-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246394

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1448926

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.4651C>T (p.R1551C) alteration is located in exon 22 (coding exon 22) of the TSPOAP1 gene. This alteration results from a C to T substitution at nucleotide position 4651, causing the arginine (R) at amino acid position 1551 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

.;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.94

.;.;L

MutationTaster

Benign

0.77

D;D;D

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.072

T;.;T

Sift4G

Uncertain

0.058

T;.;T

Polyphen

0.030

B;.;B

Vest4

0.18

MutPred

0.31

.;.;Gain of catalytic residue at P1550 (P = 0.0123);

MVP

0.18

MPC

0.29

ClinPred

0.30

GERP RS

5.2

Varity_R

0.079

gMVP

0.55

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

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