Submissions for variant NM_000489.6(ATRX):c.4130A>G (p.Glu1377Gly)

gnomAD frequency: 0.00007  dbSNP: rs782553301

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000271653	SCV000337634	uncertain significance	not provided	2015-12-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317813	SCV000850173	likely benign	Inborn genetic diseases	2018-12-02	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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000271653	SCV001251765	uncertain significance	not provided	2020-05-03	criteria provided, single submitter	clinical testing
Invitae	RCV001510472	SCV001717514	benign	Alpha thalassemia-X-linked intellectual disability syndrome	2024-01-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000271653	SCV002007796	uncertain significance	not provided	2019-07-03	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 to our knowledge
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002055056	SCV002495859	uncertain significance	Alpha thalassemia-X-linked intellectual disability syndrome; Intellectual disability-hypotonic facies syndrome, X-linked, 1	2020-12-02	criteria provided, single submitter	clinical testing	ATRX NM_000489.4 exon 13 p.Glu1377Gly (c.4130A>G): This variant has not been reported in the literature but is present in 0.01% (8/53106) of European alleles including 1 hemizygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/X-77656644-T-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:284840). Evolutionary conservation suggest that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224252	SCV003920304	uncertain significance	Acquired hemoglobin H disease; Alpha thalassemia-X-linked intellectual disability syndrome; Intellectual disability-hypotonic facies syndrome, X-linked, 1	2021-03-30	criteria provided, single submitter	clinical testing	ATRX NM_000489.4 exon 13 p.Glu1377Gly (c.4130A>G): This variant has not been reported in the literature but is present in 0.01% (8/53106) of European alleles including 1 hemizygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/X-77656644-T-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:284840). Evolutionary conservation suggest that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV000271653	SCV004165885	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	ATRX: PP2, BS2
Natera, Inc.	RCV001510472	SCV002087281	likely benign	Alpha thalassemia-X-linked intellectual disability syndrome	2020-02-25	no assertion criteria provided	clinical testing