rs765999804
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_198253.3(TERT):c.816G>A(p.Val272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000044 in 1,590,758 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: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TERT
NM_198253.3 synonymous
NM_198253.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.84
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 5-1294070-C-T is Benign according to our data. Variant chr5-1294070-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 581989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.84 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.816G>A | p.Val272= | synonymous_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.816G>A | p.Val272= | synonymous_variant | 2/15 | ||
TERT | NR_149162.3 | n.895G>A | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.895G>A | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.816G>A | p.Val272= | synonymous_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.816G>A | p.Val272= | synonymous_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.816G>A | p.Val272= | synonymous_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.816G>A | p.Val272= | synonymous_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000970 AC: 2AN: 206100Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 113098
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GnomAD4 exome AF: 0.00000139 AC: 2AN: 1438540Hom.: 0 Cov.: 35 AF XY: 0.00000280 AC XY: 2AN XY: 714552
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74362
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Jul 10, 2023 | - - |
Dyskeratosis congenita Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at