rs768168259
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_198253.3(TERT):c.2228G>A(p.Arg743Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,056 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R743W) has been classified as Uncertain significance.
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.2228G>A | p.Arg743Gln | missense_variant | 6/16 | ENST00000310581.10 | |
TERT | NM_001193376.3 | c.2228G>A | p.Arg743Gln | missense_variant | 6/15 | ||
TERT | NR_149162.3 | n.2307G>A | non_coding_transcript_exon_variant | 6/13 | |||
TERT | NR_149163.3 | n.2271G>A | non_coding_transcript_exon_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.2228G>A | p.Arg743Gln | missense_variant | 6/16 | 1 | NM_198253.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251476Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135918
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727212
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 14, 2018 | - - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 04, 2021 | - - |
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at