chr17-16217461-G-GGTAGGAGGCC
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 10P and 6B. PVS1PM2BP6_ModerateBS1
The NM_004278.4(PIGL):c.235+1_235+10dup variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.0000323 in 1,612,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PIGL
NM_004278.4 frameshift, splice_region
NM_004278.4 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.09
Genes affected
PIGL (HGNC:8966): (phosphatidylinositol glycan anchor biosynthesis class L) This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]
NCOR1 (HGNC:7672): (nuclear receptor corepressor 1) This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 17 and 20.[provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 17-16217461-G-GGTAGGAGGCC is Benign according to our data. Variant chr17-16217461-G-GGTAGGAGGCC is described in ClinVar as [Likely_benign]. Clinvar id is 2912671.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000217 (33/152220) while in subpopulation AMR AF= 0.00216 (33/15276). AF 95% confidence interval is 0.00158. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGL | NM_004278.4 | c.235+1_235+10dup | frameshift_variant, splice_region_variant | ENST00000225609.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGL | ENST00000225609.10 | c.235+1_235+10dup | frameshift_variant, splice_region_variant | 1 | NM_004278.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 250794Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135512
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459790Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9AN XY: 726244
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74364
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at