rs567983975
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_152309.3(PIK3AP1):c.1670-3T>C 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 0.00000814 in 1,597,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_152309.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.1670-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000339364.10 | |||
PIK3AP1 | XM_005269499.2 | c.1136-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
PIK3AP1 | XM_011539248.2 | c.1670-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
PIK3AP1 | XM_047424566.1 | c.1136-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.1670-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_152309.3 | P1 | |||
PIK3AP1 | ENST00000371109.3 | c.467-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
PIK3AP1 | ENST00000371110.6 | c.1136-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250458Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135488
GnomAD4 exome AF: 0.00000761 AC: 11AN: 1445348Hom.: 0 Cov.: 29 AF XY: 0.00000556 AC XY: 4AN XY: 720002
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 541752). This variant is present in population databases (rs567983975, gnomAD 0.01%). This sequence change falls in intron 10 of the PIK3AP1 gene. It does not directly change the encoded amino acid sequence of the PIK3AP1 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at