Submissions for variant NM_018451.5(CENPJ):c.3920C>T (p.Thr1307Ile)

gnomAD frequency: 0.00076  dbSNP: rs144251950

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145580	SCV000192675	uncertain significance	Microcephaly 6, primary, autosomal recessive	2013-02-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513419	SCV000608674	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	CENPJ: PP3, BS2
Fulgent Genetics, Fulgent Genetics	RCV000765126	SCV000896350	uncertain significance	Microcephaly 6, primary, autosomal recessive; Seckel syndrome 4	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001110754	SCV001268228	uncertain significance	Seckel syndrome 4	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV000145580	SCV001268229	uncertain significance	Microcephaly 6, primary, autosomal recessive	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV000513419	SCV001815039	uncertain significance	not provided	2020-08-04	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 24402816)
Invitae	RCV000513419	SCV002203356	uncertain significance	not provided	2022-10-14	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1307 of the CENPJ protein (p.Thr1307Ile). This variant is present in population databases (rs144251950, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CENPJ-related conditions. ClinVar contains an entry for this variant (Variation ID: 158214). 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 expected to disrupt CENPJ protein function. 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.
PreventionGenetics, part of Exact Sciences	RCV003905257	SCV004721863	likely benign	CENPJ-related condition	2022-01-24	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV004019766	SCV004924051	uncertain significance	Inborn genetic diseases	2021-12-07	criteria provided, single submitter	clinical testing	The c.3920C>T (p.T1307I) alteration is located in exon 17 (coding exon 16) of the CENPJ gene. This alteration results from a C to T substitution at nucleotide position 3920, causing the threonine (T) at amino acid position 1307 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000513419	SCV001800810	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000513419	SCV001967574	uncertain significance	not provided		no assertion criteria provided	clinical testing