rs199422291
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5
The NM_198253.3(TERT):c.430G>A(p.Val144Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V144V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TERT
NM_198253.3 missense
NM_198253.3 missense
Scores
5
8
5
Clinical Significance
Conservation
PhyloP100: -0.711
Publications
14 publications found
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 Gene-Disease associations (from GenCC):
- pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
- dyskeratosis congenita, autosomal dominant 2Inheritance: Unknown, SD, AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, ClinGen, Genomics England PanelApp, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
- acute myeloid leukemiaInheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- dyskeratosis congenitaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Hoyeraal-Hreidarsson syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- melanoma, cutaneous malignant, susceptibility to, 9Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-1294456-C-T is Pathogenic according to our data. Variant chr5-1294456-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 39124.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_198253.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TERT | TSL:1 MANE Select | c.430G>A | p.Val144Met | missense | Exon 2 of 16 | ENSP00000309572.5 | O14746-1 | ||
| TERT | TSL:1 | c.430G>A | p.Val144Met | missense | Exon 2 of 15 | ENSP00000334346.6 | O14746-3 | ||
| TERT | TSL:1 | n.430G>A | non_coding_transcript_exon | Exon 2 of 13 | ENSP00000425003.1 | O14746-4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1439686Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 716082
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1439686
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
716082
African (AFR)
AF:
AC:
0
AN:
33300
American (AMR)
AF:
AC:
0
AN:
44136
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25924
East Asian (EAS)
AF:
AC:
0
AN:
39446
South Asian (SAS)
AF:
AC:
0
AN:
85338
European-Finnish (FIN)
AF:
AC:
0
AN:
37036
Middle Eastern (MID)
AF:
AC:
0
AN:
5534
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109082
Other (OTH)
AF:
AC:
0
AN:
59890
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
2
-
-
not provided (2)
-
1
-
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 (1)
-
-
-
Interstitial lung disease 2 (1)
-
-
-
Pulmonary fibrosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of helix (P = 0.0696)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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