Submissions for variant NM_000295.5(SERPINA1):c.646+1G>T

gnomAD frequency: 0.00001  dbSNP: rs751235320

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169461	SCV000220891	likely pathogenic	Alpha-1-antitrypsin deficiency	2014-11-14	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000593270	SCV000706472	likely pathogenic	not provided	2017-02-21	criteria provided, single submitter	clinical testing
Invitae	RCV000169461	SCV002245454	pathogenic	Alpha-1-antitrypsin deficiency	2023-08-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Studies have shown that disruption of this splice site alters SERPINA1 gene expression (PMID: 8364536). ClinVar contains an entry for this variant (Variation ID: 189064). This variant has not been reported in the literature in individuals affected with SERPINA1-related conditions. This variant is present in population databases (rs751235320, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 2 of the SERPINA1 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 SERPINA1 are known to be pathogenic (PMID: 25425243).
Baylor Genetics	RCV000169461	SCV004203125	likely pathogenic	Alpha-1-antitrypsin deficiency	2023-07-19	criteria provided, single submitter	clinical testing
OMIM	RCV000019606	SCV000039904	other	PI NULL(WEST)	2016-07-15	no assertion criteria provided	literature only
Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital	RCV000169461	SCV000608321	pathogenic	Alpha-1-antitrypsin deficiency	2014-12-08	no assertion criteria provided	curation