rs758110675
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_198253.3(TERT):c.1393G>C(p.Val465Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,587,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. V465V) 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.1393G>C | p.Val465Leu | missense_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.1393G>C | p.Val465Leu | missense_variant | 2/15 | ||
TERT | NR_149162.3 | n.1472G>C | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.1472G>C | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.1393G>C | p.Val465Leu | missense_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.1393G>C | p.Val465Leu | missense_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.1393G>C | p.Val465Leu | missense_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.1393G>C | p.Val465Leu | missense_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000107 AC: 21AN: 196768Hom.: 0 AF XY: 0.0000374 AC XY: 4AN XY: 106920
GnomAD4 exome AF: 0.0000153 AC: 22AN: 1435296Hom.: 0 Cov.: 32 AF XY: 0.0000126 AC XY: 9AN XY: 711926
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 30, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Reported as n.1451G>C, observed in a bone marrow sample in an individual with acute myeloid leukemia (Yan et al., 2013); This variant is associated with the following publications: (PMID: 26298771, 23157242) - |
TERT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 17, 2023 | The TERT c.1393G>C variant is predicted to result in the amino acid substitution p.Val465Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.15% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-1293608-C-G). It has conflicting interpretations in ClinVar of likely benign and uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/539202/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at