Submissions for variant NM_007347.5(AP4E1):c.613C>A (p.His205Asn)

gnomAD frequency: 0.00052  dbSNP: rs148499164

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000116366	SCV000150290	uncertain significance	not provided	2014-03-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000460419	SCV000551583	uncertain significance	Spastic paraplegia	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 205 of the AP4E1 protein (p.His205Asn). This variant is present in population databases (rs148499164, gnomAD 0.07%). This missense change has been observed in individual(s) with persistent stutter (PMID: 26544806). ClinVar contains an entry for this variant (Variation ID: 128402). 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 disruptive. Experimental studies have shown that this missense change does not substantially affect AP4E1 function (PMID: 26544806). 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.
Fulgent Genetics, Fulgent Genetics	RCV000763973	SCV000894924	uncertain significance	Stuttering, familial persistent, 1; Hereditary spastic paraplegia 51	2018-10-31	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000116366	SCV001714524	uncertain significance	not provided	2021-12-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000116366	SCV001747128	uncertain significance	not provided	2021-06-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000116366	SCV001773825	uncertain significance	not provided	2021-04-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26544806)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847663	SCV002105217	uncertain significance	Hereditary spastic paraplegia	2019-09-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002514584	SCV003606746	uncertain significance	Inborn genetic diseases	2024-05-07	criteria provided, single submitter	clinical testing	(Grozeva, 2015) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.