Submissions for variant NM_025243.4(SLC19A3):c.399C>G (p.Pro133=)

dbSNP: rs138363524

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726481	SCV000344972	uncertain significance	not provided	2016-09-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001083300	SCV000428302	uncertain significance	Biotin-responsive basal ganglia disease	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000726481	SCV000527862	likely benign	not provided	2021-05-27	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000366632	SCV000615298	likely benign	not specified	2017-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001083300	SCV000762312	likely benign	Biotin-responsive basal ganglia disease	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000726481	SCV002821042	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	SLC19A3: BP4, BP7
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001083300	SCV003920477	likely benign	Biotin-responsive basal ganglia disease	2022-05-18	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.07% (51/68024) (https://gnomad.broadinstitute.org/variant/2-227699316-G-C?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Likely benign (Variation ID:290414). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.