chr5-68292303-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_181523.3(PIK3R1):c.961G>A(p.Gly321Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_181523.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.961G>A | p.Gly321Ser | missense_variant | 8/16 | ENST00000521381.6 | NP_852664.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.961G>A | p.Gly321Ser | missense_variant | 8/16 | 1 | NM_181523.3 | ENSP00000428056 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152048Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251334Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135854
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461346Hom.: 0 Cov.: 29 AF XY: 0.0000509 AC XY: 37AN XY: 726988
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152048Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74274
ClinVar
Submissions by phenotype
SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 23, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PIK3R1 protein function. ClinVar contains an entry for this variant (Variation ID: 463170). This variant has not been reported in the literature in individuals affected with PIK3R1-related conditions. This variant is present in population databases (rs142439210, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 321 of the PIK3R1 protein (p.Gly321Ser). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | PIK3R1: PS4:Supporting, BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at