rs777945799
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_024675.4(PALB2):c.3351-4T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_024675.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PALB2 | NM_024675.4 | c.3351-4T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261584.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALB2 | ENST00000261584.9 | c.3351-4T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_024675.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251014Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135742
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459970Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726470
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial cancer of breast Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 11, 2024 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at