Submissions for variant NM_000478.6(ALPL):c.744C>T (p.Asp248=)

gnomAD frequency: 0.00047  dbSNP: rs188689330

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000251117	SCV000304436	likely benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000251117	SCV000916442	likely benign	not specified	2019-08-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000913489	SCV001058637	likely benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000251117	SCV001476898	benign	not specified	2020-05-11	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000913489	SCV005258921	likely benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000913489	SCV001550423	likely benign	not provided		no assertion criteria provided	clinical testing	The ALPL p.Asp171Asp variant was not identified in the literature nor was it identified in the COGR, Cosmic, MutDB or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs188689330) and ClinVar (classified as likely benign by Prevention Genetics). The variant was identified in control databases in 78 of 282744 chromosomes at a frequency of 0.000276 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 7 of 7222 chromosomes (freq: 0.000969), Latino in 29 of 35432 chromosomes (freq: 0.000819), African in 11 of 24944 chromosomes (freq: 0.000441) and European (non-Finnish) in 31 of 129096 chromosomes (freq: 0.00024), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The p.Asp171Asp 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 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.