rs1319433657
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024675.4(PALB2):c.3163T>C(p.Tyr1055His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,438 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. Y1055C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024675.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALB2 | NM_024675.4 | c.3163T>C | p.Tyr1055His | missense_variant | 11/13 | ENST00000261584.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALB2 | ENST00000261584.9 | c.3163T>C | p.Tyr1055His | missense_variant | 11/13 | 1 | NM_024675.4 | P1 | |
ENST00000561764.1 | n.186-3558A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251252Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135816
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461438Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727024
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 04, 2021 | The p.Y1055H variant (also known as c.3163T>C), located in coding exon 11 of the PALB2 gene, results from a T to C substitution at nucleotide position 3163. The tyrosine at codon 1055 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2023 | This variant has not been reported in the literature in individuals affected with PALB2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PALB2 protein function. ClinVar contains an entry for this variant (Variation ID: 530074). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1055 of the PALB2 protein (p.Tyr1055His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at