dbSNP rs12880583: TEP1:p.His993Arg (chr14-20386079-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007110.5(TEP1):c.2978A>G(p.His993Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,608,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. H993Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

Publications

3 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04409638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.2978A>G	p.His993Arg	missense	Exon 20 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.2654A>G	p.His885Arg	missense	Exon 18 of 53	NP_001305964.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TEP1	ENST00000262715.10	TSL:1 MANE Select	c.2978A>G	p.His993Arg	missense	Exon 20 of 55	ENSP00000262715.5
TEP1	ENST00000556935.5	TSL:1	c.2654A>G	p.His885Arg	missense	Exon 18 of 53	ENSP00000452574.1
TEP1	ENST00000555008.5	TSL:1	n.1028A>G		non_coding_transcript_exon	Exon 8 of 43	ENSP00000450541.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000811

AC:

AN:

246584

AF XY:

0.00000750

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1456768

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33170

American (AMR)

AF:

0.00

AC:

AN:

43498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25942

East Asian (EAS)

AF:

0.00

AC:

AN:

39516

South Asian (SAS)

AF:

0.0000470

AC:

AN:

85184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110190

Other (OTH)

AF:

0.0000166

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.060

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.60

M_CAP

Benign

0.0041

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.30

PhyloP100

-0.17

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.77

REVEL

Benign

0.087

Sift

Benign

0.57

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.038

MutPred

0.46

Gain of solvent accessibility (P = 0.0584)

MVP

0.19

MPC

0.13

ClinPred

0.013

GERP RS

-1.9

Varity_R

0.059

gMVP

0.45

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over