rs756954938
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_198253.3(TERT):c.1130G>T(p.Arg377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. R377C) has been classified as Uncertain significance.
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
1
7
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.369
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33672976).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.1130G>T | p.Arg377Leu | missense_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.1130G>T | p.Arg377Leu | missense_variant | 2/15 | ||
TERT | NR_149162.3 | n.1209G>T | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.1209G>T | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.1130G>T | p.Arg377Leu | missense_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.1130G>T | p.Arg377Leu | missense_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.1130G>T | p.Arg377Leu | missense_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.1130G>T | p.Arg377Leu | missense_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1406464Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 694356
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1406464
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
694356
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
P;B
Vest4
MutPred
Loss of MoRF binding (P = 0.0082);Loss of MoRF binding (P = 0.0082);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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