NM_004855.5:c.18dupC
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_004855.5(PIGB):c.18dupC(p.Lys7GlnfsTer80) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PIGB
NM_004855.5 frameshift
NM_004855.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.664
Genes affected
PIGB (HGNC:8959): (phosphatidylinositol glycan anchor biosynthesis class B) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases. [provided by RefSeq, Jul 2008]
PIGBOS1 (HGNC:50696): (PIGB opposite strand 1) Involved in regulation of endoplasmic reticulum unfolded protein response. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]
RAB27A (HGNC:9766): (RAB27A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 9 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-55319267-G-GC is Pathogenic according to our data. Variant chr15-55319267-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 2992590.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PIGB | NM_004855.5 | c.18dupC | p.Lys7GlnfsTer80 | frameshift_variant | Exon 1 of 12 | ENST00000164305.10 | NP_004846.4 | |
| PIGBOS1 | NM_001308421.2 | c.-480dupG | upstream_gene_variant | ENST00000436697.3 | NP_001295350.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PIGB | ENST00000164305.10 | c.18dupC | p.Lys7GlnfsTer80 | frameshift_variant | Exon 1 of 12 | 1 | NM_004855.5 | ENSP00000164305.5 | ||
| PIGB | ENST00000566999.5 | c.18dupC | p.Lys7GlnfsTer80 | frameshift_variant | Exon 1 of 6 | 3 | ENSP00000456531.1 | |||
| PIGBOS1 | ENST00000436697.3 | c.-480dupG | upstream_gene_variant | 2 | NM_001308421.2 | ENSP00000484893.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152242
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000849 AC: 2AN: 235456Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 127924
GnomAD3 exomes
AF:
AC:
2
AN:
235456
Hom.:
AF XY:
AC XY:
2
AN XY:
127924
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1454974Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722832
GnomAD4 exome
AF:
AC:
1
AN:
1454974
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
722832
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74380
GnomAD4 genome
AF:
AC:
1
AN:
152242
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74380
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Oct 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This sequence change creates a premature translational stop signal (p.Lys7Glnfs*80) in the PIGB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIGB are known to be pathogenic (PMID: 31256876, 34400385). This variant is present in population databases (rs756195113, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PIGB-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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