Variant rs1760904 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007110.5(TEP1):c.3583T>G(p.Ser1195Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S1195P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.936

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:

TEP1 (HGNC:):

TEP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10010257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5 linkuse as main transcript	c.3583T>G	p.Ser1195Ala	missense_variant	25/55	ENST00000262715.10	NP_009041.2	Q99973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEP1	ENST00000262715.10 linkuse as main transcript	c.3583T>G	p.Ser1195Ala	missense_variant	25/55	1	NM_007110.5	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5 linkuse as main transcript	c.3259T>G	p.Ser1087Ala	missense_variant	23/53	1		ENSP00000452574.1	G3V5X7
TEP1	ENST00000555008.5 linkuse as main transcript	n.1633T>G		non_coding_transcript_exon_variant	13/43	1		ENSP00000450541.1	G3V2A4
TEP1	ENST00000555727.5 linkuse as main transcript	n.3583T>G		non_coding_transcript_exon_variant	25/54	1		ENSP00000451634.1	G3V470

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000425

AC:

AN:

235410

Hom.:

AF XY:

0.00000784

AC XY:

AN XY:

127626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448838

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720638

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.052

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.14

Sift

Benign

0.34

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0050

B;B

Vest4

0.099

MutPred

0.55

Gain of sheet (P = 0.1208);.;

MVP

0.56

MPC

0.089

ClinPred

0.058

GERP RS

4.8

Varity_R

0.044

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over