ClinVar Miner

Submissions for variant NM_001369369.1(FOXN1):c.1232G>A (p.Arg411Gln)

gnomAD frequency: 0.00003  dbSNP: rs373908977
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001423789 SCV001626373 likely benign T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2020-09-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004029889 SCV004871591 uncertain significance Inborn genetic diseases 2023-10-05 criteria provided, single submitter clinical testing The c.1232G>A (p.R411Q) alteration is located in exon 7 (coding exon 7) of the FOXN1 gene. This alteration results from a G to A substitution at nucleotide position 1232, causing the arginine (R) at amino acid position 411 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000960614 SCV001549741 likely benign not provided no assertion criteria provided clinical testing The FOXN1 p.Arg411Gln variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs373908977) and in control databases in 29 of 279436 chromosomes (1 homozygous) at a frequency of 0.000104 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 21 of 30548 chromosomes (freq: 0.000687), European (non-Finnish) in 7 of 126690 chromosomes (freq: 0.000055) and East Asian in 1 of 19916 chromosomes (freq: 0.00005), while the variant was not observed in the African, Latino, Ashkenazi Jewish, European (Finnish) or Other populations. The p.Arg411 residue is conserved in mammals but not in more distantly related organisms and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the consensus splicing sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan and GeneSplicer) do not predict a difference in splicing, while one program (NNSplice) predicts a new 3’ splice site. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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