chr7-550572-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PM5PP3_StrongBS2
The NM_001164760.2(PRKAR1B):c.1004G>A(p.Arg335Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000628 in 1,593,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R335W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001164760.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR1B | NM_001164760.2 | c.1004G>A | p.Arg335Gln | missense_variant | 11/11 | ENST00000537384.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1B | ENST00000537384.6 | c.1004G>A | p.Arg335Gln | missense_variant | 11/11 | 5 | NM_001164760.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000894 AC: 2AN: 223684Hom.: 0 AF XY: 0.00000814 AC XY: 1AN XY: 122912
GnomAD4 exome AF: 0.00000555 AC: 8AN: 1441386Hom.: 0 Cov.: 32 AF XY: 0.00000838 AC XY: 6AN XY: 716040
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PRKAR1B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 335 of the PRKAR1B protein (p.Arg335Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at