NM_003288.4:c.480C>A

Variant names:

• chr20-63889193-C-A
• NM_003288.4:c.480C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003288.4(TPD52L2):​c.480C>A​(p.Asn160Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPD52L2 NM_003288.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L2	NM_003288.4	c.480C>A	p.Asn160Lys	missense_variant	Exon 6 of 7	ENST00000346249.9	NP_003279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52L2	ENST00000346249.9	c.480C>A	p.Asn160Lys	missense_variant	Exon 6 of 7	1	NM_003288.4	ENSP00000343547.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.549C>A (p.N183K) alteration is located in exon 8 (coding exon 8) of the TPD52L2 gene. This alteration results from a C to A substitution at nucleotide position 549, causing the asparagine (N) at amino acid position 183 to be replaced by a lysine (K). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T;.;T;.;.;.;.;.
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.33	T;T;T;T;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	.;D;D;D;D;D;D;D
REVEL	Benign	0.095
Sift	Benign	0.20	.;T;T;T;T;T;T;T
Sift4G	Benign	0.26	T;T;T;T;T;T;T;T
Polyphen		0.49, 0.74, 0.47	.;.;P;.;.;P;.;P
Vest4		0.76
MutPred		0.71		.;.;Gain of methylation at N160 (P = 0.0378);.;.;.;.;.;
MVP		0.16
MPC		0.36
ClinPred		0.94	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62520546;