Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_001202543.1 | Alternative | 13882 nt | 128–4678 |
| NM_001202543.2 | Alternative | 13766 nt | 25–4575 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open""
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | -108 bp |
| Donor Loss (DL) | 0.0 | -248 bp |
| Acceptor Gain (AG) | 0.0 | -22 bp |
| Donor Gain (DG) | 0.0 | -203 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to standard ACMG guidelines, PVS1 is null variant in a gene where loss of function is a known mechanism of disease. The evidence for this variant shows it is a missense change (V1194I), not a null variant. Therefore, this criterion is not applied.
PS1 (Not Applied)
According to standard ACMG guidelines, PS1 is the same amino acid change as a known pathogenic variant regardless of nucleotide change. The evidence for this variant shows no previously established pathogenic variant at residue V1194. Therefore, this criterion is not applied.
PS2 (Not Applied)
According to standard ACMG guidelines, PS2 is de novo (both maternity and paternity confirmed) in a patient with the disease. There is no de novo data for this variant. Therefore, this criterion is not applied.
PS3 (Not Applied)
According to standard ACMG guidelines, PS3 requires well-established functional studies supportive of a damaging effect. No functional characterization exists for V1194I. Therefore, this criterion is not applied.
PS4 (Not Applied)
According to standard ACMG guidelines, PS4 is prevalence in affected individuals significantly increased compared with controls. No case-control data are available. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to standard ACMG guidelines, PM1 is located in a mutational hotspot or well-established functional domain without benign variation. Domain or hotspot data for residue V1194 are unavailable. Therefore, this criterion is not applied.
PM2 (Moderate)
According to standard ACMG guidelines, PM2 is absent from controls (or at extremely low frequency if recessive). The evidence for this variant shows a MAF of 0.00084% in gnomAD, supporting rarity. Therefore, this criterion is applied at Moderate strength because the variant is extremely rare in population databases.
PM3 (Not Applied)
According to standard ACMG guidelines, PM3 is detected in trans with a pathogenic variant for recessive disorders. No trans or zygosity data are available. Therefore, this criterion is not applied.
PM4 (Not Applied)
According to standard ACMG guidelines, PM4 is protein length changes due to in-frame deletions/insertions. This is a missense variant without length change. Therefore, this criterion is not applied.
PM5 (Not Applied)
According to standard ACMG guidelines, PM5 is a novel missense change at an amino acid residue where a different pathogenic missense change has been seen. No pathogenic missense variants at V1194 are reported. Therefore, this criterion is not applied.
PM6 (Not Applied)
According to standard ACMG guidelines, PM6 is assumed de novo without confirmation. There is no de novo information. Therefore, this criterion is not applied.
PP1 (Not Applied)
According to standard ACMG guidelines, PP1 is co-segregation with disease in multiple affected family members. No family segregation data are available. Therefore, this criterion is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines, PP2 is a missense variant in a gene with low rate of benign variation where missense is a common mechanism. Gene-specific constraint and missense mechanism data are lacking. Therefore, this criterion is not applied.
PP3 (Not Applied)
According to standard ACMG guidelines, PP3 is multiple lines of computational evidence support deleterious effect. Computational tools predominantly predict benign impact, not deleterious. Therefore, this criterion is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines, PP4 is patient's phenotype highly specific for the gene. No phenotype data are provided. Therefore, this criterion is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, PP5 is a reputable source reporting variant as pathogenic without accessible evidence. No such reports exist. Therefore, this criterion is not applied.
BA1 (Not Applied)
According to standard ACMG guidelines, BA1 is allele frequency >5% in controls. The allele frequency is far below that threshold. Therefore, this criterion is not applied.
BS1 (Not Applied)
According to standard ACMG guidelines, BS1 is allele frequency greater than expected for the disorder. The variant frequency is below thresholds for BS1. Therefore, this criterion is not applied.
BS2 (Not Applied)
According to standard ACMG guidelines, BS2 is observed in a healthy adult for a dominant disorder. No data on healthy adult carriers. Therefore, this criterion is not applied.
BS3 (Not Applied)
According to standard ACMG guidelines, BS3 is well-established functional studies show no damaging effect. No functional studies exist. Therefore, this criterion is not applied.
BS4 (Not Applied)
According to standard ACMG guidelines, BS4 is lack of segregation in affected family members. No segregation data are available. Therefore, this criterion is not applied.
BP1 (Not Applied)
According to standard ACMG guidelines, BP1 is missense variant in a gene where only loss of function causes disease. Mechanism of disease for CUX1 is not clearly established as only LoF. Therefore, this criterion is not applied.
BP2 (Not Applied)
According to standard ACMG guidelines, BP2 is observed in trans with a pathogenic variant for dominant disorders or in cis with a pathogenic variant. No phasing data. Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, BP3 is in-frame indels in a repetitive region without known function. This is a missense variant. Therefore, this criterion is not applied.
BP4 (Supporting)
According to standard ACMG guidelines, BP4 is multiple lines of computational evidence suggest no impact. The evidence for this variant shows benign predictions from CADD, MetaSVM, MetaLR, PrimateAI, low REVEL score, and SpliceAI predicts no splicing impact. Therefore, this criterion is applied at Supporting strength because computational data indicate benign effect.
BP5 (Not Applied)
According to standard ACMG guidelines, BP5 is variant found in a case with an alternate molecular basis for disease. No case reports with alternate molecular diagnoses. Therefore, this criterion is not applied.
BP6 (Not Applied)
According to standard ACMG guidelines, BP6 is a reputable source reports variant as benign without accessible evidence. No such reports exist. Therefore, this criterion is not applied.
BP7 (Not Applied)
According to standard ACMG guidelines, BP7 is synonymous variant with no predicted splicing impact. This is a missense variant. Therefore, this criterion is not applied.