ClinVar Miner

Submissions for variant NM_133261.3(GIPC3):c.856G>A (p.Val286Ile)

gnomAD frequency: 0.00126  dbSNP: rs138339125
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000150726 SCV000198146 benign not specified 2012-04-30 criteria provided, single submitter clinical testing Val286Ile in Exon 06 of GIPC3: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (26/7016) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs138339125).
Eurofins Ntd Llc (ga) RCV000724549 SCV000231813 uncertain significance not provided 2015-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000724549 SCV000618422 likely benign not provided 2020-12-10 criteria provided, single submitter clinical testing
Invitae RCV000724549 SCV001051100 likely benign not provided 2024-01-13 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003917470 SCV004736408 likely benign GIPC3-related condition 2022-11-28 criteria provided, single submitter 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).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000724549 SCV001549776 likely benign not provided no assertion criteria provided clinical testing The GIPC3 p.Val286Ile variant was not identified in the literature but was identified in dbSNP (ID: rs138339125) and ClinVar (classified as uncertain significance by GeneDx and EGL Genetics, as likely benign by Invitae and as benign by Laboratory for Molecular Medicine). The variant was identified in control databases in 326 of 273846 chromosomes (1 homozygous) at a frequency of 0.00119 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 25 of 10050 chromosomes (freq: 0.002488), European (non-Finnish) in 243 of 124586 chromosomes (freq: 0.00195), European (Finnish) in 29 of 24102 chromosomes (freq: 0.001203), Other in 6 of 6970 chromosomes (freq: 0.000861), Latino in 21 of 34498 chromosomes (freq: 0.000609) and African in 2 of 24056 chromosomes (freq: 0.000083), but was not observed in the East Asian or South Asian populations. The p.Val286 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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