16-88726546-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 10P and 4B. PVS1PP5_ModerateBS2
The NM_001142864.4(PIEZO1):c.3796+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000787 in 1,396,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001142864.4 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000130 AC: 2AN: 153606Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 81678
GnomAD4 exome AF: 0.00000787 AC: 11AN: 1396916Hom.: 0 Cov.: 35 AF XY: 0.0000102 AC XY: 7AN XY: 688824
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
The PIEZO1 c.3796+1G>A variant (rs869025599) is reported in the literature in one individual with generalized lymphatic dysplasia (Fotiou 2015). This variant is also reported in ClinVar (Variation ID: 223130). This variant is found in the Latino/Admixed American population with an allele frequency of 0.008% (2/24648 alleles) in the Genome Aggregation Database. This variant disrupts the canonical splice donor site of intron 26, which is likely to negatively impact gene function. Based on available information, this variant is considered to be pathogenic. REFERENCES Fotiou E et al. Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat Commun. 2015 PMID: 26333996 -
Lymphatic malformation 6 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at