13-45340042-C-G

Variant names:

• chr13-45340042-C-G
• NM_003295.4:c.245G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003295.4(TPT1):​c.245G>C​(p.Ser82Thr) 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: TPT1 NM_003295.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01

Genes affected

TPT1 (HGNC:12022): (tumor protein, translationally-controlled 1) This gene encodes a protein that is a regulator of cellular growth and proliferation. Its mRNA is highly structured and contains an oligopyrimidine tract (5'-TOP) in its 5' untranslated region that functions to repress its translation under quiescent conditions. The encoded protein is involved in a variety of cellular pathways, including apoptosis, protein synthesis and cell division. It binds to and stabilizes microtubules, and removal of this protein through phosphorylation is required for progression through mitotic and meiotic cell divisions. This gene is known to play a role in carcinogenesis, and is upregulated in some cancer cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

ENSG00000273149 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31461826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPT1	NM_003295.4	c.245G>C	p.Ser82Thr	missense_variant	Exon 3 of 6	ENST00000530705.6	NP_003286.1
TPT1	NM_001286272.2	c.245G>C	p.Ser82Thr	missense_variant	Exon 3 of 6		NP_001273201.1
TPT1	NM_001286273.2	c.143G>C	p.Ser48Thr	missense_variant	Exon 2 of 5		NP_001273202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPT1	ENST00000530705.6	c.245G>C	p.Ser82Thr	missense_variant	Exon 3 of 6	1	NM_003295.4	ENSP00000431872.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245G>C (p.S82T) alteration is located in exon 3 (coding exon 3) of the TPT1 gene. This alteration results from a G to C substitution at nucleotide position 245, causing the serine (S) at amino acid position 82 to be replaced by a threonine (T). 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	Benign	0.26
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;T;.;T;.;T;.
Eigen	Benign	0.048
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T;.;T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.31	T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	.;M;.;.;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	.;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.058	.;T;T;T;T;T;D
Sift4G	Benign	0.073	T;T;T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.;.;.
Vest4		0.21
MutPred		0.49		Gain of catalytic residue at Q79 (P = 0.0032);Gain of catalytic residue at Q79 (P = 0.0032);.;.;.;Gain of catalytic residue at Q79 (P = 0.0032);.;
MVP		0.14
MPC		0.36
ClinPred		0.79	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.20

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: chr13-45914177;