rs863224704
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The ENST00000507735.6(PALLD):c.1922C>T(p.Ser641Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,537,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S641S) has been classified as Likely benign.
Frequency
Consequence
ENST00000507735.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.*108C>T | 3_prime_UTR_variant | 22/22 | ENST00000505667.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALLD | ENST00000505667.6 | c.*108C>T | 3_prime_UTR_variant | 22/22 | 1 | NM_001166108.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000138 AC: 2AN: 145034Hom.: 0 AF XY: 0.0000129 AC XY: 1AN XY: 77288
GnomAD4 exome AF: 0.0000108 AC: 15AN: 1384870Hom.: 0 Cov.: 31 AF XY: 0.0000132 AC XY: 9AN XY: 683382
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74458
ClinVar
Submissions by phenotype
Pancreatic adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 21, 2018 | This sequence change replaces serine with leucine at codon 641 of the PALLD protein (p.Ser641Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PALLD-related disease. ClinVar contains an entry for this variant (Variation ID: 216535). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at