ClinVar Miner

Submissions for variant NM_014423.4(AFF4):c.1589G>T (p.Gly530Val)

gnomAD frequency: 0.00001  dbSNP: rs1411633307
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001927937 SCV002170170 uncertain significance Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 530 of the AFF4 protein (p.Gly530Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AFF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1405216). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AFF4 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
New York Genome Center RCV001927937 SCV002764508 uncertain significance Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome 2021-12-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002557580 SCV003554247 uncertain significance Inborn genetic diseases 2021-07-14 criteria provided, single submitter clinical testing The c.1589G>T (p.G530V) alteration is located in exon 11 (coding exon 10) of the AFF4 gene. This alteration results from a G to T substitution at nucleotide position 1589, causing the glycine (G) at amino acid position 530 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004749779 SCV005360704 uncertain significance AFF4-related disorder 2024-08-06 no assertion criteria provided clinical testing The AFF4 c.1589G>T variant is predicted to result in the amino acid substitution p.Gly530Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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