rs182571219
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001166108.2(PALLD):c.2695T>A(p.Ser899Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,608,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S899L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001166108.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALLD | NM_001166108.2 | c.2695T>A | p.Ser899Thr | missense_variant | 16/22 | ENST00000505667.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.2695T>A | p.Ser899Thr | missense_variant | 16/22 | 1 | NM_001166108.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251446Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135896
GnomAD4 exome AF: 0.0000481 AC: 70AN: 1455920Hom.: 0 Cov.: 29 AF XY: 0.0000511 AC XY: 37AN XY: 724722
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2022 | The p.S882T variant (also known as c.2644T>A), located in coding exon 14 of the PALLD gene, results from a T to A substitution at nucleotide position 2644. The serine at codon 882 is replaced by threonine, an amino acid with similar 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 | Dec 27, 2023 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 395 of the PALLD protein (p.Ser395Thr). This variant is present in population databases (rs182571219, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. ClinVar contains an entry for this variant (Variation ID: 476377). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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