rs754359147
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_198253.3(TERT):āc.702G>Cā(p.Leu234Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,582,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. L234L) has been classified as Likely benign.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.702G>C | p.Leu234Phe | missense_variant | 2/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.702G>C | p.Leu234Phe | missense_variant | 2/15 | ||
TERT | NR_149162.3 | n.781G>C | non_coding_transcript_exon_variant | 2/13 | |||
TERT | NR_149163.3 | n.781G>C | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.702G>C | p.Leu234Phe | missense_variant | 2/16 | 1 | NM_198253.3 | P2 | |
TERT | ENST00000334602.10 | c.702G>C | p.Leu234Phe | missense_variant | 2/15 | 1 | A2 | ||
TERT | ENST00000460137.6 | c.702G>C | p.Leu234Phe | missense_variant, NMD_transcript_variant | 2/13 | 1 | |||
TERT | ENST00000656021.1 | c.702G>C | p.Leu234Phe | missense_variant, NMD_transcript_variant | 2/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000105 AC: 2AN: 191010Hom.: 0 AF XY: 0.00000939 AC XY: 1AN XY: 106472
GnomAD4 exome AF: 0.00000210 AC: 3AN: 1430320Hom.: 0 Cov.: 35 AF XY: 0.00000282 AC XY: 2AN XY: 710106
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2022 | The p.L234F variant (also known as c.702G>C), located in coding exon 2 of the TERT gene, results from a G to C substitution at nucleotide position 702. The leucine at codon 234 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Aug 19, 2021 | The TERT c.702G>C (p.Leu234Phe) missense change has a maximum subpopulation frequency of 0.0063% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/5-1294299-C-G). This variant occurs in a gene where missense variants are more likely to be damaging based on methods described by Lek et al. (PP2; PMID: 27535533). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with clinical features of dyskeratosis congenita. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PP2, BP4. - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at