rs557697540
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000505667.6(PALLD):c.1965-12552G>C variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,514,546 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 2 hom. )
Consequence
PALLD
ENST00000505667.6 intron
ENST00000505667.6 intron
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 9.54
Genes affected
PALLD (HGNC:17068): (palladin, cytoskeletal associated protein) This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.07457653).
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PALLD | NM_001166108.2 | c.1965-12552G>C | intron_variant | ENST00000505667.6 | NP_001159580.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.1965-12552G>C | intron_variant | 1 | NM_001166108.2 | ENSP00000425556 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152192Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000627 AC: 7AN: 111722Hom.: 0 AF XY: 0.0000810 AC XY: 5AN XY: 61710
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GnomAD4 exome AF: 0.0000279 AC: 38AN: 1362236Hom.: 2 Cov.: 35 AF XY: 0.0000417 AC XY: 28AN XY: 671564
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152310Hom.: 1 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74464
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pancreatic adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 27, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 580788). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. This variant is present in population databases (rs557697540, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 160 of the PALLD protein (p.Gly160Ala). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at