rs199422289

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5

The NM_198253.3(TERT):c.97C>T(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,282,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

TERT
NM_198253.3 missense

Scores

Clinical Significance

Likely risk allele no assertion criteria provided P:1O:1

Conservation

PhyloP100: -0.485

Variant links:

Genes affected

TERT (HGNC:11730): (telomerase reverse transcriptase) Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity. [provided by RefSeq, Jul 2008]

TERT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a region_of_interest RNA-interacting domain 1 (size 229) in uniprot entity TERT_HUMAN there are 10 pathogenic changes around while only 3 benign (77%) in NM_198253.3

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-1294893-G-A is Pathogenic according to our data. Variant chr5-1294893-G-A is described in ClinVar as [Likely_risk_allele]. Clinvar id is 39127.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submissions are: {not_provided=1}. Variant chr5-1294893-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERT	NM_198253.3 link	c.97C>T	p.Pro33Ser	missense_variant	Exon 1 of 16	ENST00000310581.10	NP_937983.2	O14746-1
TERT	NM_001193376.3 link	c.97C>T	p.Pro33Ser	missense_variant	Exon 1 of 15		NP_001180305.1	O14746-3
TERT	NR_149162.3 link	n.176C>T		non_coding_transcript_exon_variant	Exon 1 of 13
TERT	NR_149163.3 link	n.176C>T		non_coding_transcript_exon_variant	Exon 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TERT	ENST00000310581.10 link	c.97C>T	p.Pro33Ser	missense_variant	Exon 1 of 16	1	NM_198253.3	ENSP00000309572.5	O14746-1
TERT	ENST00000334602.10 link	c.97C>T	p.Pro33Ser	missense_variant	Exon 1 of 15	1		ENSP00000334346.6	O14746-3
TERT	ENST00000460137.6 link	n.97C>T		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000425003.1	O14746-4
TERT	ENST00000656021.1 link	n.97C>T		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000499759.1	A0A590UK92

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000156

AC:

AN:

1282832

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

630968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.70e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary fibrosis

Pathogenic:1

Jun 09, 2022

Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center

Significance: Likely risk allele

Review Status: no assertion criteria provided

Collection Method: research

Leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted -

Interstitial lung disease 2

Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Uncertain

0.54

D;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.81

T;T

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.61

Sift

Benign

0.45

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.27

B;B

Vest4

0.28

MutPred

0.43

Gain of catalytic residue at P33 (P = 0.0859);Gain of catalytic residue at P33 (P = 0.0859);

MVP

0.95

MPC

1.1

ClinPred

0.15

GERP RS

3.0

Varity_R

0.095

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over