Submissions for variant NM_000038.6(APC):c.3876G>A (p.Thr1292=)

gnomAD frequency: 0.00004  dbSNP: rs377494451

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001705547	SCV000512073	likely benign	not provided	2019-08-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003766193	SCV000562583	likely benign	Familial adenomatous polyposis 1	2023-12-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000491341	SCV000579862	likely benign	Hereditary cancer-predisposing syndrome	2015-09-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000491341	SCV000909265	likely benign	Hereditary cancer-predisposing syndrome	2017-01-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000434349	SCV001774449	likely benign	not specified	2021-07-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003950344	SCV004762444	likely benign	APC-related disorder	2019-10-10	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).
Myriad Genetics, Inc.	RCV003766193	SCV004931781	benign	Familial adenomatous polyposis 1	2024-03-22	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Mayo Clinic Laboratories, Mayo Clinic	RCV000434349	SCV000691744	likely benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357108	SCV001552460	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC p.Thr1292= variant was not identified in the literature nor was it identified in the LOVD 3.0 and UMD-LSDB databases. The variant was identified in dbSNP (rs377494451) as “with likely benign allele and ClinVar (classified as likely benign by Invitae, GeneDx, Ambry Genetics, Color and Mayo Clinic). The variant was identified in control databases in 4 of 276,740 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 24,028 chromosomes (freq: 0.00004), Other in 1 of 6456 chromosomes (freq: 0.0002), Latino in 1 of 34,390 chromosomes (freq: 0.00003), European in 1 of 126,310 chromosomes (freq: 0.000008); it was not observed in the Ashkenazi Jewish, East Asian, Finnish and South Asian populations. The p.Thr1292= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide 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.