rs151071844
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001166108.2(PALLD):c.2980C>T(p.Arg994Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,610,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R994H) 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.2980C>T | p.Arg994Cys | missense_variant | 18/22 | ENST00000505667.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.2980C>T | p.Arg994Cys | missense_variant | 18/22 | 1 | NM_001166108.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000334 AC: 5AN: 149916Hom.: 0 Cov.: 25
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251062Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135686
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1460552Hom.: 0 Cov.: 32 AF XY: 0.0000606 AC XY: 44AN XY: 726614
GnomAD4 genome AF: 0.0000334 AC: 5AN: 149916Hom.: 0 Cov.: 25 AF XY: 0.0000274 AC XY: 2AN XY: 73026
ClinVar
Submissions by phenotype
Pancreatic adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 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 disease. This variant is present in population databases (rs151071844, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This sequence change replaces arginine with cysteine at codon 490 of the PALLD protein (p.Arg490Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at