Submissions for variant NM_033026.6(PCLO):c.1297G>A (p.Ala433Thr)

gnomAD frequency: 0.00180  dbSNP: rs201344475

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001312125	SCV001502579	likely benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	PCLO: BP4, BS2
Baylor Genetics	RCV001329544	SCV001521005	uncertain significance	Pontocerebellar hypoplasia type 3	2019-07-18	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV001312125	SCV002461563	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994262	SCV004813304	uncertain significance	not specified	2024-02-02	criteria provided, single submitter	clinical testing	Variant summary: PCLO c.1297G>A (p.Ala433Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 1613176 control chromosomes, predominantly at a frequency of 0.0059 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.1297G>A in individuals affected with Pontocerebellar Hypoplasia Type 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1013552). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV004651563	SCV005154114	likely benign	Inborn genetic diseases	2024-03-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003928838	SCV004738049	likely benign	PCLO-related disorder	2022-07-20	no assertion criteria provided	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).