Genetic Variant NM_003288.4:c.251C>T (chr20-63873753-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.251C>T(p.Ser84Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,451,592 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: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TPD52L2
NM_003288.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Publications

5 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:

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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=0.37212124).

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.251C>T	p.Ser84Phe	missense	Exon 3 of 7	NP_003279.2
TPD52L2	NM_199360.3		c.251C>T	p.Ser84Phe	missense	Exon 3 of 9	NP_955392.1	O43399-7
TPD52L2	NM_001243895.2		c.251C>T	p.Ser84Phe	missense	Exon 3 of 6	NP_001230824.1	A0A087WYR3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPD52L2	ENST00000346249.9	TSL:1 MANE Select	c.251C>T	p.Ser84Phe	missense	Exon 3 of 7	ENSP00000343547.4	O43399-1
TPD52L2	ENST00000352482.8	TSL:1	c.251C>T	p.Ser84Phe	missense	Exon 3 of 8	ENSP00000344647.4	O43399-5
TPD52L2	ENST00000348257.9	TSL:1	c.251C>T	p.Ser84Phe	missense	Exon 3 of 6	ENSP00000343554.5	O43399-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

235552

AF XY:

0.0000156

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:

0.00

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1451592

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

721990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32778

American (AMR)

AF:

0.00

AC:

AN:

42774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25848

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38848

South Asian (SAS)

AF:

0.00

AC:

AN:

84572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1107866

Other (OTH)

AF:

0.0000167

AC:

AN:

59996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Uncertain

0.42

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.58

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.030

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

PhyloP100

2.0

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.97

Vest4

0.47

MutPred

0.56

Loss of disorder (P = 0.0065)

MVP

0.15

MPC

0.59

ClinPred

0.91

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.33

gMVP

0.38

Mutation Taster

=80/20

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over