ClinVar Miner

Submissions for variant NM_014780.5(CUL7):c.4625G>A (p.Arg1542Gln)

gnomAD frequency: 0.00006  dbSNP: rs189054608
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000280737 SCV000463381 uncertain significance 3-M syndrome 2016-06-14 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000733439 SCV000861509 uncertain significance not provided 2018-06-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000733439 SCV001490651 uncertain significance not provided 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1542 of the CUL7 protein (p.Arg1542Gln). This variant is present in population databases (rs189054608, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CUL7-related conditions. ClinVar contains an entry for this variant (Variation ID: 356821). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002524480 SCV003742965 uncertain significance Inborn genetic diseases 2021-10-12 criteria provided, single submitter clinical testing The c.4625G>A (p.R1542Q) alteration is located in exon 25 (coding exon 24) of the CUL7 gene. This alteration results from a G to A substitution at nucleotide position 4625, causing the arginine (R) at amino acid position 1542 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003488570 SCV004241493 uncertain significance not specified 2023-12-14 criteria provided, single submitter clinical testing Variant summary: CUL7 c.4625G>A (p.Arg1542Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 251482 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CUL7 causing Three M Syndrome 1 (0.00014 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.4625G>A in individuals affected with Three M Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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