rs864622234
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001166108.2(PALLD):c.2333G>T(p.Gly778Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. G778G) has been classified as Likely benign.
Frequency
Consequence
NM_001166108.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALLD | NM_001166108.2 | c.2333G>T | p.Gly778Val | missense_variant | 14/22 | ENST00000505667.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.2333G>T | p.Gly778Val | missense_variant | 14/22 | 1 | NM_001166108.2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251298Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135818
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461456Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727070
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The p.G761V variant (also known as c.2282G>T), located in coding exon 12 of the PALLD gene, results from a G to T substitution at nucleotide position 2282. The glycine at codon 761 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Pancreatic adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2020 | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PALLD-related conditions. ClinVar contains an entry for this variant (Variation ID: 219755). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 274 of the PALLD protein (p.Gly274Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at