5-1280176-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_198253.3(TERT):c.1932G>A(p.Thr644=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,614,108 control chromosomes in the GnomAD database, including 1 homozygotes. 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. T644T) 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.1932G>A | p.Thr644= | synonymous_variant | 4/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.1932G>A | p.Thr644= | synonymous_variant | 4/15 | ||
TERT | NR_149162.3 | n.2011G>A | non_coding_transcript_exon_variant | 4/13 | |||
TERT | NR_149163.3 | n.2011G>A | non_coding_transcript_exon_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.1932G>A | p.Thr644= | synonymous_variant | 4/16 | 1 | NM_198253.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152246Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000123 AC: 31AN: 251346Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135862
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461744Hom.: 1 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 727160
GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152364Hom.: 0 Cov.: 34 AF XY: 0.000322 AC XY: 24AN XY: 74514
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 23, 2021 | - - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Hereditary cancer-predisposing syndrome;C0265965: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: 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. - |
Aplastic anemia;C0023467:Acute myeloid leukemia;C3151443:Dyskeratosis congenita, autosomal dominant 2;C3553617:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1;C3554574:Melanoma, cutaneous malignant, susceptibility to, 9;C4551974:Dyskeratosis congenita, autosomal dominant 1;C5561926:Interstitial lung disease 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 17, 2022 | - - |
TERT-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 30, 2022 | 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). - |
Acute myeloid leukemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at