Submissions for variant NM_030777.4(SLC2A10):c.316G>A (p.Ala106Thr)

dbSNP: rs6094438

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000756648	SCV000250698	uncertain significance	not provided	2018-10-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the SLC2A10 gene. The A106T variant has not been published as pathogenic or been reported as benign to our knowledge. The A106T variant is observed at a frequency of 0.015% (5/34,408 alleles) in individuals of Latino ancestry, and globally at a frequency of 0.008% (21/276,560 alleles), although no homozygotes were reported (Lek et al., 2016). Furthermore, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Nevertheless, the A106T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. As arterial tortuosity syndrome due to pathogenic variants in the SLC2A10 gene is an autosomal recessive disease, it is expected that an affected individual would harbor pathogenic variants in both alleles (in trans) of the SLC2A10 gene. No second pathogenic variant or variant of uncertain significance was identified by this sequence and deletion/duplication analysis. The possibility that this patient harbors a second SLC2A10 variant that is undetectable by this test cannot be excluded. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000687656	SCV000815238	likely benign	Arterial tortuosity syndrome	2024-12-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756648	SCV000884527	uncertain significance	not provided	2018-01-23	criteria provided, single submitter	clinical testing	The SLC2A10 c.316G>A; p.Ala106Thr variant (rs6094438), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a Latino population frequency of 0.01% (identified on 5 out of 34,408 chromosomes) and is classified as likely benign in ClinVar (ID: 213712). The alanine at position 106 is weakly conserved and computational analyses of the effects of the p.Ala106Thr variant on protein structure and function make conflicting predictions (SIFT: damaging, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Ala106Thr variant cannot be determined with certainty.
CeGaT Center for Human Genetics Tuebingen	RCV000756648	SCV001502392	uncertain significance	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002321791	SCV002607729	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-07-31	criteria provided, single submitter	clinical testing	The c.316G>A (p.A106T) alteration is located in exon 2 (coding exon 2) of the SLC2A10 gene. This alteration results from a G to A substitution at nucleotide position 316, causing the alanine (A) at amino acid position 106 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003488452	SCV004241689	uncertain significance	not specified	2023-12-26	criteria provided, single submitter	clinical testing