chr17-58308572-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004758.4(TSPOAP1):​c.4700C>T​(p.Ala1567Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,555,324 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: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TSPOAP1
NM_004758.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.381
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.063599735).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSPOAP1NM_004758.4 linkuse as main transcriptc.4700C>T p.Ala1567Val missense_variant 22/32 ENST00000343736.9 NP_004749.2
TSPOAP1NM_001261835.2 linkuse as main transcriptc.4700C>T p.Ala1567Val missense_variant 22/32 NP_001248764.1
TSPOAP1NM_024418.3 linkuse as main transcriptc.4520C>T p.Ala1507Val missense_variant 21/31 NP_077729.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSPOAP1ENST00000343736.9 linkuse as main transcriptc.4700C>T p.Ala1567Val missense_variant 22/321 NM_004758.4 ENSP00000345824 P2O95153-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000429
AC:
9
AN:
209840
Hom.:
0
AF XY:
0.0000621
AC XY:
7
AN XY:
112666
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:
0.000310
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000210
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000214
AC:
30
AN:
1403114
Hom.:
0
Cov.:
31
AF XY:
0.0000232
AC XY:
16
AN XY:
691046
show subpopulations
Gnomad4 AFR exome
AF:
0.0000314
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.000256
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000740
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsAug 17, 2021The c.4700C>T (p.A1567V) 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 4700, causing the alanine (A) at amino acid position 1567 to be replaced by a valine (V). 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
0.085
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0097
.;.;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.064
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;.;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.64
N;.;N
REVEL
Benign
0.099
Sift
Benign
0.36
T;.;T
Sift4G
Benign
0.51
T;.;T
Polyphen
0.021
B;.;B
Vest4
0.11
MVP
0.17
MPC
0.21
ClinPred
0.085
T
GERP RS
4.2
Varity_R
0.053
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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.

Other links and lift over

dbSNP: rs143530655; hg19: chr17-56385933; COSMIC: COSV52117950; COSMIC: COSV52117950; API