NM_003288.4:c.509G>C

Variant names:

• chr20-63889222-G-C
• rs1380400870
• NM_003288.4:c.509G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003288.4(TPD52L2):​c.509G>C​(p.Arg170Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R170Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPD52L2 NM_003288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.509G>C	p.Arg170Pro	missense	Exon 6 of 7	NP_003279.2
	TPD52L2	NM_199360.3		c.578G>C	p.Arg193Pro	missense	Exon 8 of 9	NP_955392.1	O43399-7
	TPD52L2	NM_199362.3		c.551G>C	p.Arg184Pro	missense	Exon 7 of 8	NP_955394.1	O43399-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L2	ENST00000346249.9	TSL:1 MANE Select	c.509G>C	p.Arg170Pro	missense	Exon 6 of 7	ENSP00000343547.4	O43399-1
	TPD52L2	ENST00000352482.8	TSL:1	c.551G>C	p.Arg184Pro	missense	Exon 7 of 8	ENSP00000344647.4	O43399-5
	TPD52L2	ENST00000348257.9	TSL:1	c.449G>C	p.Arg150Pro	missense	Exon 5 of 6	ENSP00000343554.5	O43399-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.041	D
Polyphen		0.94	P
Vest4		0.62
MutPred		0.60		Loss of MoRF binding (P = 0.0016)
MVP		0.21
MPC		0.72
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.68
gMVP		0.63
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1380400870; hg19: chr20-62520575;