8-80053361-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001025253.3(TPD52):c.205C>T(p.Arg69Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
TPD52
NM_001025253.3 missense
NM_001025253.3 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 1.95
Genes affected
TPD52 (HGNC:12005): (tumor protein D52) Enables calcium ion binding activity and protein homodimerization activity. Involved in B cell differentiation. Located in endoplasmic reticulum and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPD52 | NM_001025253.3 | c.205C>T | p.Arg69Trp | missense_variant | 3/8 | ENST00000518937.6 | NP_001020424.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TPD52 | ENST00000518937.6 | c.205C>T | p.Arg69Trp | missense_variant | 3/8 | 2 | NM_001025253.3 | ENSP00000429915.1 | ||
ENSG00000276418 | ENST00000522938.5 | n.325C>T | non_coding_transcript_exon_variant | 3/8 | 2 | ENSP00000430858.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152076Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
4
AN:
152076
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251264Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135800
GnomAD3 exomes
AF:
AC:
7
AN:
251264
Hom.:
AF XY:
AC XY:
5
AN XY:
135800
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461478Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727056
GnomAD4 exome
AF:
AC:
29
AN:
1461478
Hom.:
Cov.:
31
AF XY:
AC XY:
15
AN XY:
727056
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74402
GnomAD4 genome
AF:
AC:
4
AN:
152194
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74402
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
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 | Jun 28, 2023 | The c.325C>T (p.R109W) alteration is located in exon 3 (coding exon 3) of the TPD52 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;M;M;M
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
B;.;.;.;.;B
Vest4
MVP
MPC
0.39
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at