Submissions for variant NM_138422.4(ADAT3):c.430G>A (p.Val144Met)

gnomAD frequency: 0.00001  dbSNP: rs730882213

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000254727	SCV000321383	pathogenic	not provided	2025-01-24	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as p.V128M; This variant is associated with the following publications: (PMID: 32860008, 31130284, 37644014, 34374989, 26633546, 25558065, 30296593, 30529455, 31263000, 32552793, 32214227, 33101984, 28454995, 30202406, 35118659, 26842963, 23620220, 38168508)
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000162122	SCV000786718	pathogenic	Intellectual disability-strabismus syndrome		criteria provided, single submitter	research	The homozgous p.Val144Met variant was identified by our study in one individual with mental retardation. Of note, a first cousin who was noted to also have mental retardation was a carrier for this variant. The p.Val144Met variant is believed to be pathogenic based on numberous reports by other laboratories in the literature and databases.
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000162122	SCV000996290	pathogenic	Intellectual disability-strabismus syndrome		criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000162122	SCV001426529	pathogenic	Intellectual disability-strabismus syndrome		criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000162122	SCV001521996	pathogenic	Intellectual disability-strabismus syndrome	2020-06-03	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Department of Biochemistry, Faculty of Medicine, University of Khartoum	RCV000162122	SCV001547514	pathogenic	Intellectual disability-strabismus syndrome	2021-03-25	criteria provided, single submitter	research	We detected the variant NM_138422.3(ADAT3): c.430G>A (p.Val144Met, rs730882213) in two female siblings with Mental retardation, autosomal recessive 36 using whole-exome sequencing. We validated the variant's status in the patients using Sanger sequencing and detected it in a heterozygous status in their parents. Multiple reports previously classified the variant NM_138422.3(ADAT3): c.430G>A (p.Val144Met, rs730882213) as pathogenic (Alazami et al., 2013; El-Hattab et al., 2016).
Revvity Omics, Revvity	RCV000162122	SCV002022276	pathogenic	Intellectual disability-strabismus syndrome	2022-07-06	criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV000162122	SCV004099517	likely pathogenic	Intellectual disability-strabismus syndrome		criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital of Duesseldorf	RCV000162122	SCV004171164	pathogenic	Intellectual disability-strabismus syndrome		criteria provided, single submitter	not provided
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000162122	SCV004804796	likely pathogenic	Intellectual disability-strabismus syndrome	2024-03-17	criteria provided, single submitter	research
Breakthrough Genomics, Breakthrough Genomics	RCV000162122	SCV005088727	pathogenic	Intellectual disability-strabismus syndrome	2021-06-23	criteria provided, single submitter	clinical testing	This variant is predicted to be damaging by in-silico missense prediction tools (SIFT and Polyphen2). The variant (also known as V128M in literature) was previously reported in patients with intellectual disability and considered as founder mutation in the Saudi Arabian population [PMID: 26842963, 23620220, 32214227]. Functional studies using cell lines derived from intellectual disability-affected individuals showed a severe reduction in tRNA deaminase activity [PMID: 31263000].
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV004798787	SCV005420574	pathogenic	Neurodevelopmental disorder with brain abnormalities	2024-10-04	criteria provided, single submitter	research	PM3,PS3,PM2,PP3
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000162122	SCV005848182	pathogenic	Intellectual disability-strabismus syndrome	2025-02-18	criteria provided, single submitter	clinical testing
OMIM	RCV000162122	SCV000082799	pathogenic	Intellectual disability-strabismus syndrome	2013-07-01	no assertion criteria provided	literature only
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000162122	SCV000196407	likely pathogenic	Intellectual disability-strabismus syndrome	2014-12-01	no assertion criteria provided	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000162122	SCV001132975	pathogenic	Intellectual disability-strabismus syndrome	2019-08-25	no assertion criteria provided	clinical testing
Section for Clinical Neurogenetics, University of Tübingen	RCV000162122	SCV001156076	pathogenic	Intellectual disability-strabismus syndrome	2019-08-01	no assertion criteria provided	research
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000254727	SCV001977665	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000254727	SCV001979423	likely pathogenic	not provided		no assertion criteria provided	clinical testing