chr5-1294048-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_198253.3(TERT):c.838G>A(p.Glu280Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,592,554 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. E280E) has been classified as Likely benign.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.838G>A | p.Glu280Lys | missense_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.838G>A | p.Glu280Lys | missense_variant | 2/15 | ||
TERT | NR_149162.3 | n.917G>A | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.917G>A | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.838G>A | p.Glu280Lys | missense_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.838G>A | p.Glu280Lys | missense_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.838G>A | p.Glu280Lys | missense_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.838G>A | p.Glu280Lys | missense_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152200Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000283 AC: 60AN: 211656Hom.: 0 AF XY: 0.000250 AC XY: 29AN XY: 115854
GnomAD4 exome AF: 0.000124 AC: 178AN: 1440236Hom.: 1 Cov.: 35 AF XY: 0.000117 AC XY: 84AN XY: 715408
GnomAD4 genome AF: 0.000204 AC: 31AN: 152318Hom.: 0 Cov.: 34 AF XY: 0.000242 AC XY: 18AN XY: 74486
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 15, 2021 | Reported in an individual with DC and a positive family history, and in another individual with reported telomere disease in the published literature (Yamaguchi et al., 2015; Kapuria et al., 2019), however, additional clinical and segregation information was not included; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in 0.0276% (67/243010 alleles) in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32150348, 30523342, 30791107, 26329388) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 19, 2019 | - - |
Interstitial lung disease 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Dyskeratosis congenita Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 15, 2021 | - - |
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