NM_176787.5:c.1869A>G
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_176787.5(PIGN):c.1869A>G(p.Ala623Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,408,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
PIGN
NM_176787.5 synonymous
NM_176787.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.53
Publications
1 publications found
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]
PIGN Gene-Disease associations (from GenCC):
- multiple congenital anomalies-hypotonia-seizures syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
- Fryns syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 18-62102893-T-C is Benign according to our data. Variant chr18-62102893-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 539566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.53 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_176787.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PIGN | NM_176787.5 | MANE Select | c.1869A>G | p.Ala623Ala | synonymous | Exon 21 of 31 | NP_789744.1 | ||
| PIGN | NM_001438896.1 | c.1869A>G | p.Ala623Ala | synonymous | Exon 21 of 32 | NP_001425825.1 | |||
| PIGN | NM_012327.6 | c.1869A>G | p.Ala623Ala | synonymous | Exon 20 of 30 | NP_036459.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PIGN | ENST00000640252.2 | TSL:1 MANE Select | c.1869A>G | p.Ala623Ala | synonymous | Exon 21 of 31 | ENSP00000492233.1 | ||
| PIGN | ENST00000400334.7 | TSL:1 | c.1869A>G | p.Ala623Ala | synonymous | Exon 20 of 30 | ENSP00000383188.2 | ||
| PIGN | ENST00000638424.1 | TSL:5 | n.1869A>G | non_coding_transcript_exon | Exon 19 of 29 | ENSP00000491963.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.0000259 AC: 5AN: 192904 AF XY: 0.00000968 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
192904
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000114 AC: 16AN: 1408958Hom.: 0 Cov.: 25 AF XY: 0.00000859 AC XY: 6AN XY: 698186 show subpopulations
GnomAD4 exome
AF:
AC:
16
AN:
1408958
Hom.:
Cov.:
25
AF XY:
AC XY:
6
AN XY:
698186
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31562
American (AMR)
AF:
AC:
0
AN:
36568
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25000
East Asian (EAS)
AF:
AC:
0
AN:
38264
South Asian (SAS)
AF:
AC:
0
AN:
77448
European-Finnish (FIN)
AF:
AC:
0
AN:
51882
Middle Eastern (MID)
AF:
AC:
0
AN:
5670
European-Non Finnish (NFE)
AF:
AC:
16
AN:
1083966
Other (OTH)
AF:
AC:
0
AN:
58598
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
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5
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1
Oct 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
not provided Benign:1
Sep 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
PIGN: BP4, BP7
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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