rs375454175
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_198253.3(TERT):c.1983G>A(p.Leu661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,550,744 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L661L) has been classified as Likely benign.
Frequency
Consequence
NM_198253.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.1983G>A | p.Leu661= | synonymous_variant | 5/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.1983G>A | p.Leu661= | synonymous_variant | 5/15 | ||
TERT | NR_149162.3 | n.2062G>A | non_coding_transcript_exon_variant | 5/13 | |||
TERT | NR_149163.3 | n.2062G>A | non_coding_transcript_exon_variant | 5/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.1983G>A | p.Leu661= | synonymous_variant | 5/16 | 1 | NM_198253.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000326 AC: 5AN: 153248Hom.: 0 AF XY: 0.0000244 AC XY: 2AN XY: 82100
GnomAD4 exome AF: 0.0000150 AC: 21AN: 1398410Hom.: 0 Cov.: 33 AF XY: 0.0000145 AC XY: 10AN XY: 689978
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74500
ClinVar
Submissions by phenotype
TERT-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Hereditary cancer-predisposing syndrome;C0265965:Dyskeratosis congenita Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 26, 2022 | This alteration is classified as likely benign based on a combination of the following: 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. - |
Dyskeratosis congenita Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 14, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at