5-1294052-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_198253.3(TERT):c.834C>A(p.Pro278Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000251 in 1,590,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_198253.3 synonymous
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.834C>A | p.Pro278Pro | synonymous_variant | Exon 2 of 16 | ENST00000310581.10 | NP_937983.2 | |
TERT | NM_001193376.3 | c.834C>A | p.Pro278Pro | synonymous_variant | Exon 2 of 15 | NP_001180305.1 | ||
TERT | NR_149162.3 | n.913C>A | non_coding_transcript_exon_variant | Exon 2 of 13 | ||||
TERT | NR_149163.3 | n.913C>A | non_coding_transcript_exon_variant | Exon 2 of 13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.834C>A | p.Pro278Pro | synonymous_variant | Exon 2 of 16 | 1 | NM_198253.3 | ENSP00000309572.5 | ||
TERT | ENST00000334602.10 | c.834C>A | p.Pro278Pro | synonymous_variant | Exon 2 of 15 | 1 | ENSP00000334346.6 | |||
TERT | ENST00000460137.6 | n.834C>A | non_coding_transcript_exon_variant | Exon 2 of 13 | 1 | ENSP00000425003.1 | ||||
TERT | ENST00000656021.1 | n.834C>A | non_coding_transcript_exon_variant | Exon 2 of 17 | ENSP00000499759.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000636 AC: 13AN: 204504Hom.: 0 AF XY: 0.0000446 AC XY: 5AN XY: 112004
GnomAD4 exome AF: 0.0000236 AC: 34AN: 1438470Hom.: 0 Cov.: 35 AF XY: 0.0000196 AC XY: 14AN XY: 714472
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74362
ClinVar
Submissions by phenotype
Aplastic anemia Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
p.Pro278Pro in exon 2 of TERT: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 3/25580 European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs375423906). -
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
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Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Dyskeratosis congenita Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at