rs12326381
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_176787.5(PIGN):c.1962G>A(p.Leu654=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,456,732 control chromosomes in the GnomAD database, including 36,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2947 hom., cov: 31)
Exomes 𝑓: 0.22 ( 33565 hom. )
Consequence
PIGN
NM_176787.5 synonymous
NM_176787.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.52
Genes affected
PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 18-62102800-C-T is Benign according to our data. Variant chr18-62102800-C-T is described in ClinVar as [Benign]. Clinvar id is 403301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.52 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.1962G>A | p.Leu654= | synonymous_variant | 21/31 | ENST00000640252.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.1962G>A | p.Leu654= | synonymous_variant | 21/31 | 1 | NM_176787.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.171 AC: 25968AN: 152014Hom.: 2946 Cov.: 31
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GnomAD3 exomes AF: 0.166 AC: 29527AN: 177866Hom.: 3113 AF XY: 0.166 AC XY: 15716AN XY: 94490
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GnomAD4 exome AF: 0.217 AC: 283249AN: 1304598Hom.: 33565 Cov.: 18 AF XY: 0.216 AC XY: 140140AN XY: 649912
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GnomAD4 genome ? AF: 0.171 AC: 25975AN: 152134Hom.: 2947 Cov.: 31 AF XY: 0.168 AC XY: 12491AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at