rs141425941
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198253.3(TERT):c.2371G>A(p.Val791Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,611,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2371G>A | p.Val791Ile | missense_variant | 7/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.2371G>A | p.Val791Ile | missense_variant | 7/15 | ||
TERT | NR_149162.3 | n.2366-3563G>A | intron_variant, non_coding_transcript_variant | ||||
TERT | NR_149163.3 | n.2330-3563G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.2371G>A | p.Val791Ile | missense_variant | 7/16 | 1 | NM_198253.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000898 AC: 22AN: 245078Hom.: 0 AF XY: 0.000120 AC XY: 16AN XY: 133560
GnomAD4 exome AF: 0.000162 AC: 237AN: 1459416Hom.: 0 Cov.: 32 AF XY: 0.000172 AC XY: 125AN XY: 725842
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74492
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal dominant 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 13, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Aug 30, 2023 | The TERT c.2371G>A (p.Val791Ile) missense change has a maximum subpopulation frequency of 0.016% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function and functional studies suggest that this variant alone does not affect TERT function (PMID: 21483807). This variant occurs in a gene where missense variants are more likely to be damaging based on methods described by Lek et al. (PMID: 27535533). This variant has been reported in an individual with aplastic anemia (PMID: 26136524). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Apr 04, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2020 | Published functional studies demonstrate no damaging effect: TERT protein activity similar to wild type when studied independently (Alder 2011); Observed in individuals with aplastic anemia (Ghemlas 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function This variant is associated with the following publications: (PMID: 31871297, 26136524, 23538340, 24798238, 21483807, 26851889, 22900168) - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at