Submissions for variant NM_004615.4(TSPAN7):c.515C>A (p.Pro172His)

gnomAD frequency: 0.00126  dbSNP: rs104894951

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000721059	SCV000851944	uncertain significance	History of neurodevelopmental disorder	2012-10-12	criteria provided, single submitter	clinical testing	In published studies involving a family with six affected males with non-syndromic X-linked mental retardation, this variant was present in all individuals with mental retardation and in one male whose IQ score is within the normal range (Zemni R et al. Nat Genet. 2000;24(2):167-170 and Gomot M et al. Am J Med Genet. 2002;112:400-404). In a separate study, this variant was observed in 1/105 males with mental retardation, and it was absent in this particular proband's unaffected brother (Maranduba CM et al. Am J Med Genet. 2004;124A:413-415). This variant has not been detected in conjunction with a pathogenic mutation to date.Based on data from the NHLBI Exome Sequencing Project (ESP), the A-allele has an overall frequency of approximately 0.05% (1/1997) in male alleles studied. The A-allele was observed in 0.07% (1/1475) of European American male alleles but was absent in 522 African American male alleles and was not observed in the homozygous state in 3381 female alleles studied (http://snp.gs.washington.edu/EVS). Furthermore, this variant was not detected in a total of 420 normal X chromosomes in all of the published studies. This amino acid position is not conserved on species alignment.This alteration is predicted to be benign with a score of 0.327 (sensitivity: 0.86; specificity: 0.76)This alteration is predicted to be tolerated with a score of 0.190 (conservation: 1.91)
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000012396	SCV000883120	likely benign	Intellectual disability, X-linked 58	2018-11-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000904077	SCV001048575	likely benign	not provided	2018-12-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000012396	SCV001141830	uncertain significance	Intellectual disability, X-linked 58	2019-05-28	criteria provided, single submitter	clinical testing
OMIM	RCV000012396	SCV000032630	uncertain significance	Intellectual disability, X-linked 58	2004-02-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000904077	SCV001930624	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000904077	SCV001974174	likely benign	not provided		no assertion criteria provided	clinical testing