Submissions for variant NM_015650.4(TRAF3IP1):c.988-1G>C

gnomAD frequency: 0.00001  dbSNP: rs372499275

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857884	SCV002191523	likely pathogenic	not provided	2024-06-06	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 6 of the TRAF3IP1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TRAF3IP1 are known to be pathogenic (PMID: 21945076, 26487268, 29068549). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with short-rib polydactyly syndrome (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 446656). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003409730	SCV004107608	likely pathogenic	TRAF3IP1-related disorder	2023-06-13	criteria provided, single submitter	clinical testing	The TRAF3IP1 c.988-1G>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was reported in an individual with short rib-polydactyly syndrome, type 2 (Zhang et al. 2018. PubMed ID: 29068549). This variant is reported in 0.00094% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-239242600-G-C). Variants that disrupt the consensus splice acceptor site in TRAF3IP1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Dan Cohn Lab, University Of California Los Angeles	RCV000515883	SCV000612074	pathogenic	Short-rib thoracic dysplasia 6 with or without polydactyly	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515883	SCV001479589	likely pathogenic	Short-rib thoracic dysplasia 6 with or without polydactyly		no assertion criteria provided	research