NM_003036.4(SKI):c.347G>A (p.Gly116Glu) AND Shprintzen-Goldberg syndrome

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jun 13, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000030816.38

Allele description [Variation Report for NM_003036.4(SKI):c.347G>A (p.Gly116Glu)]

NM_003036.4(SKI):c.347G>A (p.Gly116Glu)

Gene:

SKI:SKI proto-oncogene [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_003036.4(SKI):c.347G>A (p.Gly116Glu)

HGVS:

NC_000001.11:g.2229113G>A
NG_013084.1:g.5419G>A
NM_003036.4:c.347G>AMANE SELECT
NP_003027.1:p.Gly116Glu
NC_000001.10:g.2160552G>A
NM_003036.3:c.347G>A
P12755:p.Gly116Glu

Protein change:

G116E; GLY116GLU

Links:

UniProtKB: P12755#VAR_071182; OMIM: 164780.0001; dbSNP: rs387907303

NCBI 1000 Genomes Browser:

rs387907303

Molecular consequence:

NM_003036.4:c.347G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Shprintzen-Goldberg syndrome (SGS)
Synonyms:: Shprintzen-Goldberg craniosynostosis syndrome; Craniosynostosis with arachnodactyly and abdominal hernias; Marfanoid disorder with craniosynostosis type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008426; MedGen: C1321551; Orphanet: 2462; OMIM: 182212

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000053491	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000266519	Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine	criteria provided, single submitter (Submitter's publication)	Pathogenic	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV001366746	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 27, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001375519	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23023332, 24357594, 28492532

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	1	not provided	not provided	no	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.

Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E, Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, Caulfield MJ, Scott AF, Destrée A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS, et al.

Nat Genet. 2012 Nov;44(11):1249-54. doi: 10.1038/ng.2421. Epub 2012 Sep 30.

PubMed [citation]

PMID:: 23023332
PMCID:: PMC3545695

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000053491.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 43-year-old woman with Shprintzen-Goldberg craniosynostosis syndrome (SGS; 182212), Doyle et al. (2012) identified heterozygosity for a de novo 347G-A transition in exon 1 of the SKI gene, resulting in a gly116-to-glu (G116E) substitution at a highly conserved residue in an exposed beta hairpin loop in the DHD domain. The mutation was not found in her unaffected parents or in SNP databases.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine, SCV000266519.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	1	not provided

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001366746.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001375519.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SKI protein function. ClinVar contains an entry for this variant (Variation ID: 37258). This missense change has been observed in individual(s) with Shprintzen-Goldberg syndrome (PMID: 23023332, 24357594). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 116 of the SKI protein (p.Gly116Glu).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine