Genetic Variant TPD52:c.-347C>T (chr8-80064518-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000519303.6(TPD52):c.-347C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000238 in 1,613,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

TPD52
ENST00000519303.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

Variant links:

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]

TPD52 links:

ENSG00000276418 (HGNC:):

ENSG00000276418 links:

Genome browser will be placed here

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=0.13754165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52	NM_001025253.3 link	c.95C>T	p.Ser32Leu	missense_variant	Exon 2 of 8	ENST00000518937.6	NP_001020424.1	P55327-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52	ENST00000518937.6 link	c.95C>T	p.Ser32Leu	missense_variant	Exon 2 of 8	2	NM_001025253.3	ENSP00000429915.1		P55327-4
ENSG00000276418	ENST00000522938.5 link	n.215C>T		non_coding_transcript_exon_variant	Exon 2 of 8	2		ENSP00000430858.2		H0YC42

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000191

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000227

AC:

AN:

251310

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000244

AC:

357

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000177

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215C>T (p.S72L) alteration is located in exon 2 (coding exon 2) of the TPD52 gene. This alteration results from a C to T substitution at nucleotide position 215, causing the serine (S) at amino acid position 72 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

.;.;.;.;.;T

Eigen

Benign

0.012

Eigen_PC

Benign

-0.0017

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.9

.;M;.;M;M;M

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.1

D;D;D;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

0.30

B;.;.;.;.;P

Vest4

0.57

MVP

0.53

MPC

0.28

ClinPred

0.14

GERP RS

4.1

Varity_R

0.40

gMVP

0.29

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