17-68512530-C-T
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_002734.5(PRKAR1A):c.-25C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000466 in 152,256 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 Uncertain significance (★).
Frequency
Consequence
NM_002734.5 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
Publications
- Acrodysostosis 1 with or without hormone resistanceInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- acrodysostosis with multiple hormone resistanceInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
- Carney complex, type 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- pigmented nodular adrenocortical disease, primary, 1Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
- acrodysostosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Carney complexInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial atrial myxomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- primary pigmented nodular adrenocortical diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKAR1A | NM_002734.5 | c.-25C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 11 | ENST00000589228.6 | NP_002725.1 | ||
PRKAR1A | NM_002734.5 | c.-25C>T | 5_prime_UTR_variant | Exon 1 of 11 | ENST00000589228.6 | NP_002725.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000589228.6 | c.-25C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 11 | 1 | NM_002734.5 | ENSP00000464977.2 | |||
PRKAR1A | ENST00000589228.6 | c.-25C>T | 5_prime_UTR_variant | Exon 1 of 11 | 1 | NM_002734.5 | ENSP00000464977.2 |
Frequencies
GnomAD3 genomes AF: 0.000467 AC: 71AN: 152140Hom.: 0 Cov.: 32 show subpopulations
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 2506Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 1770
GnomAD4 genome AF: 0.000466 AC: 71AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35AN XY: 74452 show subpopulations
ClinVar
Submissions by phenotype
Acrodysostosis 1 with or without hormone resistance 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. -
Carney complex, type 1 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at