rs778471055
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001166108.2(PALLD):āc.2815G>Cā(p.Val939Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V939I) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALLD | NM_001166108.2 | c.2815G>C | p.Val939Leu | missense_variant | 17/22 | ENST00000505667.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.2815G>C | p.Val939Leu | missense_variant | 17/22 | 1 | NM_001166108.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251148Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135722
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461552Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727102
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74450
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 04, 2023 | The p.V922L variant (also known as c.2764G>C), located in coding exon 15 of the PALLD gene, results from a G to C substitution at nucleotide position 2764. The valine at codon 922 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 18, 2022 | 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 C25"). ClinVar contains an entry for this variant (Variation ID: 410615). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. This variant is present in population databases (rs778471055, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 435 of the PALLD protein (p.Val435Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at