20-63873813-G-T

Variant names:

• chr20-63873813-G-T
• rs769696045
• NM_003288.4:c.311G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003288.4(TPD52L2):​c.311G>T​(p.Ser104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,545,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S104N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TPD52L2 NM_003288.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.312
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.155898).

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.311G>T	p.Ser104Ile	missense	Exon 3 of 7	NP_003279.2
	TPD52L2	NM_199360.3		c.311G>T	p.Ser104Ile	missense	Exon 3 of 9	NP_955392.1	O43399-7
	TPD52L2	NM_001243895.2		c.311G>T	p.Ser104Ile	missense	Exon 3 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.311G>T	p.Ser104Ile	missense	Exon 3 of 7	ENSP00000343547.4	O43399-1
	TPD52L2	ENST00000352482.8	TSL:1	c.311G>T	p.Ser104Ile	missense	Exon 3 of 8	ENSP00000344647.4	O43399-5
	TPD52L2	ENST00000348257.9	TSL:1	c.311G>T	p.Ser104Ile	missense	Exon 3 of 6	ENSP00000343554.5	O43399-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392872 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688888

African (AFR) AF: 0.00 AC: 0 AN: 30290

American (AMR) AF: 0.00 AC: 0 AN: 29042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23810

East Asian (EAS) AF: 0.00 AC: 0 AN: 36520

South Asian (SAS) AF: 0.00 AC: 0 AN: 76368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082488

Other (OTH) AF: 0.00 AC: 0 AN: 57560

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.059	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.31
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.089
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		0.15	B
Vest4		0.35
MutPred		0.52		Loss of disorder (P = 0.002)
MVP		0.068
MPC		0.23
ClinPred		0.83	D
GERP RS		-7.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Varity_R		0.23
gMVP		0.25
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs769696045; hg19: chr20-62505166;