rs45560936
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001040716.2(PC):c.2224-9T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,607,666 control chromosomes in the GnomAD database, including 2,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Consequence
NM_001040716.2 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PC | NM_001040716.2 | c.2224-9T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000393960.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PC | ENST00000393960.7 | c.2224-9T>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001040716.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0355 AC: 5402AN: 152072Hom.: 152 Cov.: 33
GnomAD3 exomes AF: 0.0407 AC: 9881AN: 242584Hom.: 268 AF XY: 0.0436 AC XY: 5763AN XY: 132330
GnomAD4 exome AF: 0.0490 AC: 71328AN: 1455476Hom.: 1940 Cov.: 33 AF XY: 0.0491 AC XY: 35592AN XY: 724286
GnomAD4 genome ? AF: 0.0355 AC: 5404AN: 152190Hom.: 152 Cov.: 33 AF XY: 0.0339 AC XY: 2521AN XY: 74398
ClinVar
Submissions by phenotype
Pyruvate carboxylase deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2012 | 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. - |
not provided Benign:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 19, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at