Submissions for variant NM_078480.3(PUF60):c.449_457del (p.Ala150_Phe152del)

dbSNP: rs1131692232

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000495893	SCV000583967	pathogenic	8q24.3 microdeletion syndrome	2017-06-07	criteria provided, single submitter	research
Ambry Genetics	RCV000624628	SCV000741065	pathogenic	Inborn genetic diseases	2024-02-16	criteria provided, single submitter	clinical testing	The c.449_457delCCCCCTTTG (p.A150_F152delL) alteration, located in coding exon 6 of the PUF60 gene, results from an in-frame deletion of 9 nucleotides at positions c.449 to c.457. This results in the deletion of 3 amino acids between codons 150 and 152. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in multiple individuals with features consistent with Verheij syndrome (Brea-Fernández, 2022; Grimes, 2023; Ambry internal data). Additionally, this variant has been detected in one individual with developmental delay and intellectual disability, feeding difficulties, narrow palpebral fissures, prominent forehead, wide nasal bridge, joint laxity, and polydactyly (Fennell, 2022). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000495893	SCV004009633	likely pathogenic	8q24.3 microdeletion syndrome	2023-05-17	criteria provided, single submitter	research
GeneDx	RCV003314599	SCV004014150	pathogenic	not provided	2023-07-15	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (gnomAD); In-frame deletion of 3 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 27535533, 36134573, 37303278)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003314599	SCV005839970	pathogenic	not provided	2024-11-04	criteria provided, single submitter	clinical testing	This variant, c.449_457del, results in the deletion of 3 amino acid(s) of the PUF60 protein (p.Ala150_Phe152del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of PUF60-related conditions (PMID: 33057194, 35322241, 35982159, 36134573, 36367278, 37303278). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 430808). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV000495893	SCV001428361	pathogenic	8q24.3 microdeletion syndrome	2019-01-01	no assertion criteria provided	clinical testing
Molecular Genetics laboratory, Necker Hospital	RCV003314599	SCV004031261	likely pathogenic	not provided	2018-07-09	no assertion criteria provided	clinical testing
Solve-RD Consortium	RCV000495893	SCV005200059	likely pathogenic	8q24.3 microdeletion syndrome	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team