Variant 8-80038123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001025253.3(TPD52):c.617G>A(p.Ser206Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TPD52
NM_001025253.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.475

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:

TPD52-MRPS28 (HGNC:):

TPD52-MRPS28 links:

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=0.018949777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPD52	NM_001025253.3 linkuse as main transcript	c.617G>A	p.Ser206Asn	missense_variant	8/8	ENST00000518937.6
TPD52-MRPS28	NM_001387778.1 linkuse as main transcript	c.435+4497G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPD52	ENST00000518937.6 linkuse as main transcript	c.617G>A	p.Ser206Asn	missense_variant	8/8	2	NM_001025253.3		P55327-4

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000956

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251318

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000677

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461714

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000322

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000196

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:

0.000946

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.000416

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 07, 2022

The c.668G>A (p.S223N) alteration is located in exon 6 (coding exon 6) of the TPD52 gene. This alteration results from a G to A substitution at nucleotide position 668, causing the serine (S) at amino acid position 223 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

0.065

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.64

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.18

T;T;T;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.019

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;N;N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.37

N;N;N;N;N;N;N

REVEL

Benign

0.093

Sift

Benign

0.11

T;T;T;T;T;D;D

Sift4G

Benign

0.20

T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;B;.

Vest4

0.049

MVP

0.31

MPC

0.24

ClinPred

0.047

GERP RS

1.3

Varity_R

0.054

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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