5-1271209-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_198253.3(TERT):c.2383-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,609,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_198253.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2383-5C>T | splice_region_variant, intron_variant | Intron 7 of 15 | ENST00000310581.10 | NP_937983.2 | ||
TERT | NM_001193376.3 | c.2383-5C>T | splice_region_variant, intron_variant | Intron 7 of 14 | NP_001180305.1 | |||
TERT | NR_149162.3 | n.2366-2576C>T | intron_variant | Intron 6 of 12 | ||||
TERT | NR_149163.3 | n.2330-2576C>T | intron_variant | Intron 6 of 12 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152268Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247148Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134630
GnomAD4 exome AF: 0.0000350 AC: 51AN: 1457364Hom.: 0 Cov.: 30 AF XY: 0.0000331 AC XY: 24AN XY: 725094
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:1
The c.2383-5C>T intronic variant results from a C to T substitution 5 nucleotides upstream from coding exon 8 in the TERT gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear. -
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at