Submissions for variant NM_145698.5(ACBD5):c.1467G>A (p.Trp489Ter)

dbSNP: rs1564574359

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760804	SCV000890699	pathogenic	not provided	2018-10-19	criteria provided, single submitter	clinical testing	The W489X pathogenic variant in the ACBD5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W489X variant is not observed in large population cohorts (Lek et al., 2016). We interpret W489X as a pathogenic variant.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252230	SCV002523107	uncertain significance	See cases	2021-03-25	criteria provided, single submitter	clinical testing	ACMG classification criteria: PM2, PP5
Labcorp Genetics (formerly Invitae), Labcorp	RCV000760804	SCV003314112	pathogenic	not provided	2022-08-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp489*) in the ACBD5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACBD5 are known to be pathogenic (PMID: 23105016, 27799409). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 620428). This premature translational stop signal has been observed in individual(s) with retinal dystrophy and leukodystrophy (PMID: 33427402). This variant is not present in population databases (gnomAD no frequency).