rs772236690
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000235.4(LIPA):c.538+6T>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000828 in 1,448,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000235.4 splice_region, intron
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIPA | NM_000235.4 | c.538+6T>C | splice_region_variant, intron_variant | Intron 5 of 9 | ENST00000336233.10 | NP_000226.2 | ||
LIPA | NM_001127605.3 | c.538+6T>C | splice_region_variant, intron_variant | Intron 5 of 9 | NP_001121077.1 | |||
LIPA | NM_001288979.2 | c.190+6T>C | splice_region_variant, intron_variant | Intron 3 of 7 | NP_001275908.1 | |||
LIPA | XM_024448023.2 | c.538+6T>C | splice_region_variant, intron_variant | Intron 5 of 9 | XP_024303791.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251324Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135844
GnomAD4 exome AF: 0.00000617 AC: 8AN: 1296556Hom.: 0 Cov.: 20 AF XY: 0.00000612 AC XY: 4AN XY: 654032
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74400
ClinVar
Submissions by phenotype
Wolman disease Uncertain:1
This sequence change falls in intron 5 of the LIPA gene. It does not directly change the encoded amino acid sequence of the LIPA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs772236690, gnomAD 0.009%). This variant has been observed in individual(s) with severe dyslipidemia and/or liver steatosis (PMID: 28502505). ClinVar contains an entry for this variant (Variation ID: 557809). 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 may disrupt the consensus splice site. 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. -
Lysosomal acid lipase deficiency Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at