rs770855063
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_152309.3(PIK3AP1):c.113G>T(p.Arg38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. R38C) has been classified as Likely benign.
Frequency
Consequence
NM_152309.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.113G>T | p.Arg38Leu | missense_variant | 2/17 | ENST00000339364.10 | |
PIK3AP1 | XM_011539248.2 | c.113G>T | p.Arg38Leu | missense_variant | 2/16 | ||
PIK3AP1 | XM_047424566.1 | c.-422G>T | 5_prime_UTR_variant | 3/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.113G>T | p.Arg38Leu | missense_variant | 2/17 | 1 | NM_152309.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248614Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135132
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461312Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 726950
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2023 | The c.113G>T (p.R38L) alteration is located in exon 2 (coding exon 2) of the PIK3AP1 gene. This alteration results from a G to T substitution at nucleotide position 113, causing the arginine (R) at amino acid position 38 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2021 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs770855063, ExAC 0.06%) but has not been reported in the literature in individuals with a PIK3AP1-related disease. This sequence change replaces arginine with leucine at codon 38 of the PIK3AP1 protein (p.Arg38Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at