Submissions for variant NM_001042492.3(NF1):c.3197+3A>G

gnomAD frequency: 0.00001  dbSNP: rs1359512152

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002317268	SCV000670548	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-01-13	criteria provided, single submitter	clinical testing	The c.3197+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 24 in the NF1 gene. This nucleotide position is well conserved on limited sequence alignment. In silico splice site analysis for this alteration is inconclusive; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV000681288	SCV000808750	uncertain significance	not provided	2020-07-24	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858322	SCV002215205	uncertain significance	Neurofibromatosis, type 1	2025-01-19	criteria provided, single submitter	clinical testing	This sequence change falls in intron 24 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 484108). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with inconclusive levels of altered splicing (internal data). 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.
Genome-Nilou Lab	RCV001858322	SCV002560276	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483533	SCV002778887	uncertain significance	Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis	2021-11-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000681288	SCV005437041	uncertain significance	not provided	2024-11-01	criteria provided, single submitter	clinical testing