Genetic Variant TPT1:p.Lys164Lys (chr13-45338684-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_003295.4(TPT1):c.492G>A(p.Lys164Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,613,412 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 8 hom. )

Consequence

TPT1
NM_003295.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

Variant links:

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]

TPT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 13-45338684-C-T is Benign according to our data. Variant chr13-45338684-C-T is described in ClinVar as [Benign]. Clinvar id is 734326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS2

High AC in GnomAd4 at 321 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPT1	NM_003295.4 link	c.492G>A	p.Lys164Lys	synonymous_variant	Exon 5 of 6	ENST00000530705.6	NP_003286.1	P13693-1A0A0P1J1R0
TPT1	NM_001286272.2 link	c.492G>A	p.Lys164Lys	synonymous_variant	Exon 5 of 6		NP_001273201.1	A0A0B4J2C3
TPT1	NM_001286273.2 link	c.390G>A	p.Lys130Lys	synonymous_variant	Exon 4 of 5		NP_001273202.1	P13693-2A0A024RDY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPT1	ENST00000530705.6 link	c.492G>A	p.Lys164Lys	synonymous_variant	Exon 5 of 6	1	NM_003295.4	ENSP00000431872.2		P13693-1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00357

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00206

AC:

515

AN:

250508

Hom.:

AF XY:

0.00208

AC XY:

282

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000921

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

AF:

0.00315

AC:

4599

AN:

1461178

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2268

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.000651

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000813

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00378

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152234

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00357

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00204

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00421

EpiControl

AF:

0.00415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over