Submissions for variant NM_213622.4(STAMBP):c.112C>T (p.Arg38Cys)

gnomAD frequency: 0.00009  dbSNP: rs143739249

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000043574	SCV000195120	pathogenic	Microcephaly-capillary malformation syndrome	2013-12-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000426675	SCV000517314	likely pathogenic	not provided	2023-06-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23542699, 32929933, 35723786, 35962715, 33149276)
SIB Swiss Institute of Bioinformatics	RCV000043574	SCV000803509	likely pathogenic	Microcephaly-capillary malformation syndrome	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Likely Pathogenic, for Microcephaly-capillary malformation syndrome, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:23542699). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:23542699). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Supporting => PS4 downgraded in strength to Supporting (PMID:23542699).
CeGaT Center for Human Genetics Tuebingen	RCV000426675	SCV001248156	pathogenic	not provided	2017-07-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000426675	SCV001447691	likely pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000426675	SCV003271218	pathogenic	not provided	2022-08-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 50793). This missense change has been observed in individual(s) with microcephaly-capillary malformation syndrome (PMID: 23542699). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs143739249, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 38 of the STAMBP protein (p.Arg38Cys).
OMIM	RCV000043574	SCV000071444	pathogenic	Microcephaly-capillary malformation syndrome	2013-05-01	no assertion criteria provided	literature only
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000043574	SCV001739508	pathogenic	Microcephaly-capillary malformation syndrome		no assertion criteria provided	clinical testing