chr20-63882781-C-T

Variant names:

• chr20-63882781-C-T
• rs2052951481
• NM_003288.4:c.437C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003288.4(TPD52L2):​c.437C>T​(p.Thr146Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPD52L2 NM_003288.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64
• Publications: 0 publications found

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]

ENSG00000290226 (HGNC:):

ACMG classification

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=0.3706032).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L2	NM_003288.4	MANE Select	c.437C>T	p.Thr146Ile	missense	Exon 5 of 7	NP_003279.2
	TPD52L2	NM_199360.3		c.437C>T	p.Thr146Ile	missense	Exon 5 of 9	NP_955392.1	O43399-7
	TPD52L2	NM_001243895.2		c.437C>T	p.Thr146Ile	missense	Exon 5 of 6	NP_001230824.1	A0A087WYR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L2	ENST00000346249.9	TSL:1 MANE Select	c.437C>T	p.Thr146Ile	missense	Exon 5 of 7	ENSP00000343547.4	O43399-1
	TPD52L2	ENST00000352482.8	TSL:1	c.437C>T	p.Thr146Ile	missense	Exon 5 of 8	ENSP00000344647.4	O43399-5
	TPD52L2	ENST00000348257.9	TSL:1	c.377C>T	p.Thr126Ile	missense	Exon 4 of 6	ENSP00000343554.5	O43399-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.93	P
Vest4		0.43
MutPred		0.43		Loss of loop (P = 0.0203)
MVP		0.22
MPC		0.53
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.39
gMVP		0.58
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs2052951481; hg19: chr20-62514134;