17-68524007-CT-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6BS2_Supporting
The NM_002734.5(PRKAR1A):c.441-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002734.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR1A | NM_002734.5 | c.441-5del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000589228.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000589228.6 | c.441-5del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002734.5 | P1 | |||
ENST00000590353.1 | n.620-5del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251388Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135868
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461718Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727162
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74354
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 12, 2021 | Variant summary: PRKAR1A c.441-5delT alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251388 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.441-5delT in individuals affected with Carney Complex and no experimental evidence demonstrating its impact on protein function have been reported. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as llikely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2023 | See Variant Classification Assertion Criteria. - |
Carney complex, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at