NM_022464.5(SIL1):c.1030-9G>A AND Marinesco-Sjögren syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Mar 17, 2024
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:: RCV001782768.10

Allele description

NM_022464.5(SIL1):c.1030-9G>A

Gene:

SIL1:SIL1 nucleotide exchange factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_022464.5(SIL1):c.1030-9G>A

HGVS:

NC_000005.10:g.138947482C>T
NG_008112.2:g.255895G>A
NM_001037633.2:c.1030-9G>A
NM_022464.5:c.1030-9G>AMANE SELECT
NC_000005.9:g.138283171C>T
NG_008112.1:g.255895G>A
NM_001037633.1:c.1030-9G>A
NM_001037633.2:c.1030-9G>A
NM_022464.4:c.1030-9G>A

Links:

dbSNP: rs370290043

NCBI 1000 Genomes Browser:

rs370290043

Molecular consequence:

NM_001037633.2:c.1030-9G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_022464.5:c.1030-9G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Marinesco-Sjögren syndrome (MSS)
Synonyms:: Marinesco-Garland Syndrome; Marinesco-Sjogren Syndrome-Hypergonadotrophic Hypogonadism; Marinesco-Sjogren Syndrome-Myopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009567; MedGen: C0024814; Orphanet: 559; OMIM: 248800

Recent activity

Clear Turn Off Turn On

vitelline membrane outer layer protein 1 homolog isoform 4 precursor [Homo sapie...
vitelline membrane outer layer protein 1 homolog isoform 4 precursor [Homo sapiens]
gi|222144307|ref|NP_001138413.1|

Protein

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
SCV002022584	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003244158	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24473200, 31130284, 32552793, 28492532
SCV003927905	Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	no assertion criteria provided	Pathogenic (Apr 1, 2023)	germline	clinical testing
SCV004805025	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2024)	germline	research	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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, research

Citations

PubMed

SIL1, a causative cochaperone gene of Marinesco-Söjgren syndrome, plays an essential role in establishing the architecture of the developing cerebral cortex.

Inaguma Y, Hamada N, Tabata H, Iwamoto I, Mizuno M, Nishimura YV, Ito H, Morishita R, Suzuki M, Ohno K, Kumagai T, Nagata K.

EMBO Mol Med. 2014 Mar;6(3):414-29. doi: 10.1002/emmm.201303069. Epub 2014 Jan 28.

PubMed [citation]

PMID:: 24473200
PMCID:: PMC3958314

Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.

Monies D, Abouelhoda M, Assoum M, Moghrabi N, Rafiullah R, Almontashiri N, Alowain M, Alzaidan H, Alsayed M, Subhani S, Cupler E, Faden M, Alhashem A, Qari A, Chedrawi A, Aldhalaan H, Kurdi W, Khan S, Rahbeeni Z, Alotaibi M, Goljan E, Elbardisy H, et al.

Am J Hum Genet. 2019 Jun 6;104(6):1182-1201. doi: 10.1016/j.ajhg.2019.04.011. Epub 2019 May 23. Erratum in: Am J Hum Genet. 2019 Oct 3;105(4):879. doi: 10.1016/j.ajhg.2019.09.019.

PubMed [citation]

PMID:: 31130284
PMCID:: PMC6562004

See all PubMed Citations (5)

Details of each submission

From Revvity Omics, Revvity, SCV002022584.3

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

#	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

From Invitae, SCV003244158.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change falls in intron 9 of the SIL1 gene. It does not directly change the encoded amino acid sequence of the SIL1 protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs370290043, gnomAD 0.009%). This variant has been observed in individual(s) with clinical features of Marinesco-Sjogren syndrome (PMID: 24473200, 31130284). ClinVar contains an entry for this variant (Variation ID: 280106). Studies have shown that this variant results in activation of a de novo splice site and introduces a new termination codon (PMID: 32552793). However the mRNA is not expected to undergo nonsense-mediated decay. This variant disrupts a region of the SIL1 protein in which other variant(s) (p.Leu373Cysfs*33) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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

From Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), SCV003927905.1

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

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004805025.2

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

#	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: Apr 6, 2024

ClinVar

Relating variation to medicine