Genetic Variant TPD52L2:p.Ser166Leu (chr20-63889210-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003288.4(TPD52L2):c.497C>T(p.Ser166Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000905 in 1,613,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

TPD52L2
NM_003288.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Publications

13 publications found

Variant links:

Genes affected

TPD52L2 (HGNC:12007): (TPD52 like 2) This gene encodes a member of the tumor protein D52-like family. These proteins are characterized by an N-terminal coiled-coil motif that is used to form homo- and heteromeric complexes with other tumor protein D52-like proteins. Expression of this gene may be a marker for breast cancer and acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 12. [provided by RefSeq, Aug 2011]

TPD52L2 links:

ENSG00000290226 (HGNC:):

ENSG00000290226 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4182214).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003288.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPD52L2	NM_003288.4	MANE Select	c.497C>T	p.Ser166Leu	missense	Exon 6 of 7	NP_003279.2
TPD52L2	NM_199360.3		c.566C>T	p.Ser189Leu	missense	Exon 8 of 9	NP_955392.1	O43399-7
TPD52L2	NM_199362.3		c.539C>T	p.Ser180Leu	missense	Exon 7 of 8	NP_955394.1	O43399-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPD52L2	ENST00000346249.9	TSL:1 MANE Select	c.497C>T	p.Ser166Leu	missense	Exon 6 of 7	ENSP00000343547.4	O43399-1
TPD52L2	ENST00000352482.8	TSL:1	c.539C>T	p.Ser180Leu	missense	Exon 7 of 8	ENSP00000344647.4	O43399-5
TPD52L2	ENST00000348257.9	TSL:1	c.437C>T	p.Ser146Leu	missense	Exon 5 of 6	ENSP00000343554.5	O43399-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000184

AC:

AN:

249790

AF XY:

0.000207

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 FIN exome

AF:

0.000512

Gnomad NFE exome

AF:

0.000301

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000890

AC:

130

AN:

1461202

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

85978

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000899

AC:

100

AN:

1111732

Other (OTH)

AF:

0.000215

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.079

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.0

PhyloP100

6.8

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.029

Polyphen

0.86

Vest4

0.66

MVP

0.20

MPC

0.28

ClinPred

0.68

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.77

gMVP

0.68

Mutation Taster

=52/48

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over