15-55340667-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004855.5(PIGB):c.902C>T(p.Thr301Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T301T) has been classified as Likely benign.
Frequency
Consequence
NM_004855.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGB | NM_004855.5 | c.902C>T | p.Thr301Ile | missense_variant | 8/12 | ENST00000164305.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGB | ENST00000164305.10 | c.902C>T | p.Thr301Ile | missense_variant | 8/12 | 1 | NM_004855.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 151972Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000686 AC: 17AN: 247796Hom.: 0 AF XY: 0.0000819 AC XY: 11AN XY: 134388
GnomAD4 exome AF: 0.0000801 AC: 117AN: 1460814Hom.: 0 Cov.: 31 AF XY: 0.0000840 AC XY: 61AN XY: 726582
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 151972Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74210
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2021 | The c.902C>T (p.T301I) alteration is located in exon 8 (coding exon 8) of the PIGB gene. This alteration results from a C to T substitution at nucleotide position 902, causing the threonine (T) at amino acid position 301 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 301 of the PIGB protein (p.Thr301Ile). This variant is present in population databases (rs374803936, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with PIGB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at