rs746281705
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_198253.3(TERT):c.144C>T(p.Arg48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 1,307,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
TERT
NM_198253.3 synonymous
NM_198253.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.458
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP7
?
Synonymous conserved (PhyloP=-0.458 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.144C>T | p.Arg48= | synonymous_variant | 1/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.144C>T | p.Arg48= | synonymous_variant | 1/15 | ||
TERT | NR_149162.3 | n.223C>T | non_coding_transcript_exon_variant | 1/13 | |||
TERT | NR_149163.3 | n.223C>T | non_coding_transcript_exon_variant | 1/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.144C>T | p.Arg48= | synonymous_variant | 1/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.144C>T | p.Arg48= | synonymous_variant | 1/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.144C>T | p.Arg48= | synonymous_variant, NMD_transcript_variant | 1/13 | 1 | |||
TERT | ENST00000656021.1 | c.144C>T | p.Arg48= | synonymous_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.0000155 AC: 1AN: 64456Hom.: 0 AF XY: 0.0000269 AC XY: 1AN XY: 37166
GnomAD3 exomes
AF:
AC:
1
AN:
64456
Hom.:
AF XY:
AC XY:
1
AN XY:
37166
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000230 AC: 3AN: 1307094Hom.: 0 Cov.: 34 AF XY: 0.00000311 AC XY: 2AN XY: 642936
GnomAD4 exome
AF:
AC:
3
AN:
1307094
Hom.:
Cov.:
34
AF XY:
AC XY:
2
AN XY:
642936
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2018 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TERT-related disease. While this variant is present in population databases (rs746281705), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change affects codon 48 of the TERT mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TERT protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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