Genetic Variant NM_007110.5:c.5315G>A (chr14-20378791-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007110.5(TEP1):c.5315G>A(p.Arg1772Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,614,140 control chromosomes in the GnomAD database, including 2,556 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R1772W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.040 ( 166 hom., cov: 33)

Exomes 𝑓: 0.054 ( 2390 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.547

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037632883).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5 link	c.5315G>A	p.Arg1772Gln	missense_variant	Exon 37 of 55	ENST00000262715.10	NP_009041.2	Q99973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10 link	c.5315G>A	p.Arg1772Gln	missense_variant	Exon 37 of 55	1	NM_007110.5	ENSP00000262715.5		Q99973-1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6052

AN:

152194

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0330

Gnomad ASJ

AF:

0.0717

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0842

Gnomad FIN

AF:

0.0676

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.0459

GnomAD2 exomes

AF:

0.0490

AC:

12305

AN:

251234

AF XY:

0.0529

show subpopulations

Gnomad AFR exome

AF:

0.00868

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.0750

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0671

Gnomad NFE exome

AF:

0.0547

Gnomad OTH exome

AF:

0.0515

GnomAD4 exome

AF:

0.0538

AC:

78628

AN:

1461828

Hom.:

2390

Cov.:

AF XY:

0.0551

AC XY:

40073

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00812

AC:

272

AN:

33480

American (AMR)

AF:

0.0255

AC:

1141

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0747

AC:

1953

AN:

26134

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.0831

AC:

7165

AN:

86250

European-Finnish (FIN)

AF:

0.0635

AC:

3389

AN:

53404

Middle Eastern (MID)

AF:

0.0695

AC:

401

AN:

5768

European-Non Finnish (NFE)

AF:

0.0551

AC:

61245

AN:

1111974

Other (OTH)

AF:

0.0505

AC:

3051

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

4278

8556

12835

17113

21391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2304

4608

6912

9216

11520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0397

AC:

6049

AN:

152312

Hom.:

166

Cov.:

AF XY:

0.0408

AC XY:

3042

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0102

AC:

425

AN:

41580

American (AMR)

AF:

0.0330

AC:

505

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0717

AC:

249

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0839

AC:

405

AN:

4828

European-Finnish (FIN)

AF:

0.0676

AC:

717

AN:

10608

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0530

AC:

3604

AN:

68020

Other (OTH)

AF:

0.0455

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

307

614

921

1228

1535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0492

Hom.:

632

Bravo

AF:

0.0348

TwinsUK

AF:

0.0580

AC:

215

ALSPAC

AF:

0.0514

AC:

198

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.0578

AC:

497

ExAC

AF:

0.0494

AC:

6001

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0556

EpiControl

AF:

0.0564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

PhyloP100

0.55

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.27

Sift

Benign

0.16

T;T

Sift4G

Uncertain

0.017

D;D

Polyphen

1.0

D;D

Vest4

0.12

MPC

0.22

ClinPred

0.011

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.20

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over