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). Synonymous variant affecting the same amino acid position (i.e. V791V) has been classified as Likely benign.
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 | 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 29, 2024 | - - |
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