rs373500403
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001166108.2(PALLD):c.2687G>A(p.Arg896Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,584 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R896W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001166108.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALLD | NM_001166108.2 | c.2687G>A | p.Arg896Gln | missense_variant | 16/22 | ENST00000505667.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.2687G>A | p.Arg896Gln | missense_variant | 16/22 | 1 | NM_001166108.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251432Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135888
GnomAD4 exome AF: 0.0000288 AC: 42AN: 1459346Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22AN XY: 726164
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74430
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 01, 2022 | The p.R879Q variant (also known as c.2636G>A), located in coding exon 14 of the PALLD gene, results from a G to A substitution at nucleotide position 2636. The arginine at codon 879 is replaced by glutamine, an amino acid with highly 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 | Mar 19, 2022 | This variant is present in population databases (rs373500403, gnomAD 0.03%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). ClinVar contains an entry for this variant (Variation ID: 238606). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 392 of the PALLD protein (p.Arg392Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at