Variant chr17-58325709-C-T 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.575G>A(p.Ser192Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

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:

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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=0.08198464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPOAP1	NM_004758.4 link	c.575G>A	p.Ser192Asn	missense_variant	4/32	ENST00000343736.9	NP_004749.2	O95153-1B7ZVZ7B2RUT8A7E2C5
TSPOAP1	NM_001261835.2 link	c.575G>A	p.Ser192Asn	missense_variant	4/32		NP_001248764.1	O95153B7ZVZ7X5DQQ3A7E2C5
TSPOAP1	NM_024418.3 link	c.570+584G>A		intron_variant			NP_077729.1	O95153-2B7ZVZ7B2RUT8
TSPOAP1-AS1	NR_038410.1 link	n.260C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9 link	c.575G>A	p.Ser192Asn	missense_variant	4/32	1	NM_004758.4	ENSP00000345824.4		O95153-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452902

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 27, 2021

The c.575G>A (p.S192N) alteration is located in exon 4 (coding exon 4) of the TSPOAP1 gene. This alteration results from a G to A substitution at nucleotide position 575, causing the serine (S) at amino acid position 192 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.011

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.78

M_CAP

Benign

0.0074

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.61

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.070

REVEL

Benign

0.078

Sift

Benign

0.25

Sift4G

Benign

0.66

Polyphen

0.0020

Vest4

0.25

MutPred

0.17

Gain of catalytic residue at S192 (P = 0.0203);

MVP

0.22

MPC

0.20

ClinPred

0.35

GERP RS

2.8

Varity_R

0.068

gMVP

0.067

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