Variant rs1760897 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007110.5(TEP1):c.346T>C(p.Ser116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,613,824 control chromosomes in the GnomAD database, including 87,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10842 hom., cov: 31)

Exomes 𝑓: 0.32 ( 76379 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.652

Variant links:

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TEP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.303092E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5 link	c.346T>C	p.Ser116Pro	missense_variant	2/55	ENST00000262715.10	NP_009041.2	Q99973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEP1	ENST00000262715.10 link	c.346T>C	p.Ser116Pro	missense_variant	2/55	1	NM_007110.5	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5 link	c.346T>C	p.Ser116Pro	missense_variant	2/53	1		ENSP00000452574.1	G3V5X7
TEP1	ENST00000555727.5 link	n.346T>C		non_coding_transcript_exon_variant	2/54	1		ENSP00000451634.1	G3V470
TEP1	ENST00000556549.1 link	c.346T>C	p.Ser116Pro	missense_variant	2/2	3		ENSP00000452240.1	G3V591

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55381

AN:

151832

Hom.:

10817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.331

AC:

83278

AN:

251460

Hom.:

14589

AF XY:

0.329

AC XY:

44741

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.320

AC:

467312

AN:

1461874

Hom.:

76379

Cov.:

AF XY:

0.321

AC XY:

233328

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.497

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.365

AC:

55436

AN:

151950

Hom.:

10842

Cov.:

AF XY:

0.362

AC XY:

26872

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.365

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.321

Hom.:

20004

Bravo

AF:

0.376

TwinsUK

AF:

0.309

AC:

1144

ALSPAC

AF:

0.316

AC:

1218

ESP6500AA

AF:

0.510

AC:

2249

ESP6500EA

AF:

0.318

AC:

2731

ExAC

AF:

0.334

AC:

40511

Asia WGS

AF:

0.305

AC:

1058

AN:

3478

EpiCase

AF:

0.312

EpiControl

AF:

0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.24

DANN

Benign

0.086

DEOGEN2

Benign

0.038

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.12

T;T;T

MetaRNN

Benign

0.000083

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.2

N;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.010

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.062

MPC

0.14

ClinPred

0.0013

GERP RS

-0.63

Varity_R

0.086

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over