13-45339532-T-C

Variant names:

• chr13-45339532-T-C
• rs768020738
• NM_003295.4:c.364A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_003295.4(TPT1):​c.364A>G​(p.Ile122Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000068 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPT1 NM_003295.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.88

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.116375834).
• BP6: Variant 13-45339532-T-C is Benign according to our data. Variant chr13-45339532-T-C is described in ClinVar as [Benign]. Clinvar id is 2672289.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPT1	NM_003295.4	c.364A>G	p.Ile122Val	missense_variant	Exon 4 of 6	ENST00000530705.6	NP_003286.1
TPT1	NM_001286272.2	c.364A>G	p.Ile122Val	missense_variant	Exon 4 of 6		NP_001273201.1
TPT1	NM_001286273.2	c.262A>G	p.Ile88Val	missense_variant	Exon 3 of 5		NP_001273202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPT1	ENST00000530705.6	c.364A>G	p.Ile122Val	missense_variant	Exon 4 of 6	1	NM_003295.4	ENSP00000431872.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.000112 AC: 28 AN: 249312 Hom.: 0 AF XY: 0.000134 AC XY: 18 AN XY: 134706

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000585

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000400

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000681 AC: 99 AN: 1454322 Hom.: 1 Cov.: 30 AF XY: 0.0000928 AC XY: 67 AN XY: 722278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000269

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000624

Gnomad4 OTH exome AF: 0.0000499

GnomAD4 genome Cov.: 33

Alfa AF: 0.000814 Hom.: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 12, 2023

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.17	.;T;.;T;.;T;.
Eigen	Benign	0.046
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.83	T;T;.;T;D;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.13	.;N;.;.;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.20	.;N;N;N;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.87	.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0	.;B;.;.;.;.;.
Vest4		0.22
MVP		0.12
MPC		0.34
ClinPred		0.054	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs768020738; hg19: chr13-45913667;