Genetic Variant NM_007110.5:c.346T>C (chr14-20408094-A-G) – 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.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. 15/21 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. S116C) has been classified as Uncertain significance.

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

Publications

37 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=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 rank	MANE	Protein	UniProt
TEP1	NM_007110.5 link	c.346T>C	p.Ser116Pro	missense_variant	Exon 2 of 55	ENST00000262715.10	NP_009041.2	Q99973-1

Ensembl

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

GnomAD2 exomes

AF:

0.331

AC:

83278

AN:

251460

AF XY:

0.329

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 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

African (AFR)

AF:

0.497

AC:

16653

AN:

33480

American (AMR)

AF:

0.371

AC:

16585

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

10786

AN:

26136

East Asian (EAS)

AF:

0.187

AC:

7440

AN:

39700

South Asian (SAS)

AF:

0.378

AC:

32624

AN:

86258

European-Finnish (FIN)

AF:

0.286

AC:

15284

AN:

53420

Middle Eastern (MID)

AF:

0.337

AC:

1941

AN:

5768

European-Non Finnish (NFE)

AF:

0.311

AC:

346177

AN:

1111994

Other (OTH)

AF:

0.328

AC:

19822

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

21620

43240

64859

86479

108099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11498

22996

34494

45992

57490

<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:

0.365

AC:

55436

AN:

151950

Hom.:

10842

Cov.:

AF XY:

0.362

AC XY:

26872

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.501

AC:

20760

AN:

41414

American (AMR)

AF:

0.339

AC:

5175

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1413

AN:

3468

East Asian (EAS)

AF:

0.185

AC:

958

AN:

5168

South Asian (SAS)

AF:

0.365

AC:

1753

AN:

4806

European-Finnish (FIN)

AF:

0.291

AC:

3078

AN:

10562

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21070

AN:

67958

Other (OTH)

AF:

0.364

AC:

765

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1726

3453

5179

6906

8632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.327

Hom.:

37873

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

(source)

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;.;.

PhyloP100

-0.65

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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