NM_003036.4(SKI):c.91T>C (p.Ser31Pro) AND Shprintzen-Goldberg syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000853353.1

Allele description [Variation Report for NM_003036.4(SKI):c.91T>C (p.Ser31Pro)]

NM_003036.4(SKI):c.91T>C (p.Ser31Pro)

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.91T>C (p.Ser31Pro)

HGVS:

NC_000001.11:g.2228857T>C
NG_013084.1:g.5163T>C
NM_003036.4:c.91T>CMANE SELECT
NP_003027.1:p.Ser31Pro
NC_000001.10:g.2160296T>C
NM_003036.3:c.91T>C

Protein change:

S31P

Links:

dbSNP: rs1569656981

NCBI 1000 Genomes Browser:

rs1569656981

Molecular consequence:

NM_003036.4:c.91T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000996219	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 29, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000996219

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 29, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	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

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV000996219.1

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

Description

This variant has not been previously reported or functionally characterized in the literature to our knowledge. However, a different missense variant involving the same amino acid residue (p.Ser31Leu) has been reported in a patient with Shprintzen-Goldberg syndrome (PMID: 23103230). The c.91T>C (p.Ser31Pro) variant detected in this individual localizes to the R-SMAD transcription factor binding domain and is situated in close proximity to multiple variants previously reported in patients with Shprintzen-Goldberg syndrome (PMID: 23103230, 23023332). This variant is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. It affects an amino acid that is highly conserved among vertebrates and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.91T>C (p.Ser31Pro) variant is classified as pathogenic.

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

Last Updated: Apr 23, 2022

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