rs59633770
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001166108.2(PALLD):c.3256C>T(p.Leu1086Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0011 in 1,614,110 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001166108.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00136 AC: 207AN: 152172Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00211 AC: 531AN: 251098Hom.: 5 AF XY: 0.00206 AC XY: 279AN XY: 135694
GnomAD4 exome AF: 0.00107 AC: 1571AN: 1461820Hom.: 16 Cov.: 32 AF XY: 0.00107 AC XY: 779AN XY: 727230
GnomAD4 genome AF: 0.00136 AC: 207AN: 152290Hom.: 1 Cov.: 32 AF XY: 0.00163 AC XY: 121AN XY: 74460
ClinVar
Submissions by phenotype
not specified Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Pancreatic cancer, susceptibility to, 1 Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Pancreatic adenocarcinoma Benign:1
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PALLD-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at