rs890346822
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_198253.3(TERT):c.513C>T(p.Cys171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,440 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 Likely benign (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
TERT
NM_198253.3 synonymous
NM_198253.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0380
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 -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 5-1294373-G-A is Benign according to our data. Variant chr5-1294373-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 539244.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.038 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.513C>T | p.Cys171= | synonymous_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.513C>T | p.Cys171= | synonymous_variant | 2/15 | ||
TERT | NR_149162.3 | n.592C>T | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.592C>T | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.513C>T | p.Cys171= | synonymous_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.513C>T | p.Cys171= | synonymous_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.513C>T | p.Cys171= | synonymous_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.513C>T | p.Cys171= | synonymous_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.00000550 AC: 1AN: 181952Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 101616
GnomAD3 exomes
AF:
AC:
1
AN:
181952
Hom.:
AF XY:
AC XY:
0
AN XY:
101616
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: 7.02e-7 AC: 1AN: 1424440Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 707338
GnomAD4 exome
AF:
AC:
1
AN:
1424440
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
707338
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: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2023 | - - |
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