NM_001164760.2:c.1069C>T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001164760.2(PRKAR1B):c.1069C>T(p.Arg357Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000552 in 1,449,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001164760.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000444 AC: 1AN: 225340Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 122142
GnomAD4 exome AF: 0.00000552 AC: 8AN: 1449432Hom.: 0 Cov.: 31 AF XY: 0.00000695 AC XY: 5AN XY: 719774
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Marbach-Schaaf neurodevelopmental syndrome Uncertain:1
The missense variant c.1069C>T (p.Arg357Cys) in the PRKAR1B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.0004%) in the gnomAD Exomes. The amino acid Arginine at position 357 is changed to a Cysteine changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen - Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Arg357Cys in PRKAR1B is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at