VCV000160049.35 - ClinVar

NM_001048166.1(STIL):c.1136C>T (p.Ser379Phe)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(3); Benign(1); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001048166.1(STIL):c.1136C>T (p.Ser379Phe)

Variation ID: 160049 Accession: VCV000160049.35

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p33 1: 47282457 (GRCh38) [ NCBI UCSC ] 1: 47748129 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 23, 2014	Oct 20, 2024	Jan 12, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001048166.1:c.1136C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001041631.1:p.Ser379Phe	missense
NM_001282936.1:c.1136C>T	NP_001269865.1:p.Ser379Phe	missense
NM_001282937.1:c.1136C>T	NP_001269866.1:p.Ser379Phe	missense
NM_001282938.1:c.995C>T	NP_001269867.1:p.Ser332Phe	missense
NM_001282939.1:c.995C>T	NP_001269868.1:p.Ser332Phe	missense
NM_003035.2:c.1136C>T	NP_003026.2:p.Ser379Phe	missense
NC_000001.11:g.47282457G>A
NC_000001.10:g.47748129G>A
NG_012126.1:g.36691C>T

... more HGVS ... less HGVS

Protein change

S379F, S332F

Other names

Canonical SPDI

NC_000001.11:47282456:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00060 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00225

Exome Aggregation Consortium (ExAC) 0.00242

Trans-Omics for Precision Medicine (TOPMed) 0.00246

The Genome Aggregation Database (gnomAD) 0.00258

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00292

1000 Genomes Project 30x 0.00047

1000 Genomes Project 0.00060

Links

dbSNP: rs149185431 ClinGen: CA239544 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
STIL		-	-	GRCh38 GRCh37	380	389

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jan 12, 2024	RCV000887897.24
Microcephaly 7, primary, autosomal recessive	Uncertain significance (4)	criteria provided, multiple submitters, no conflicts	May 23, 2017	RCV000147679.12
not specified	Benign (1)	criteria provided, single submitter	Nov 16, 2016	RCV000174071.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Jan 12, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001031488.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Uncertain significance (May 23, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Microcephaly 7, primary, autosomal recessive Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000611524.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014
Likely benign (Dec 30, 2019)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV001474801.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021	Publications: PubMed (2) PubMed: 26548919‚ 23772360
Uncertain significance (Dec 28, 2012)	criteria provided, single submitter (ACMG Guidelines, 2007) Method: clinical testing	Microcephaly 7, primary, autosomal recessive (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000195130.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014
Benign (Nov 16, 2016)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000225307.5 First in ClinVar: Jun 29, 2015 Last updated: Jun 29, 2015	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=STIL Number of individuals with the variant: 2 Sex: mixed
Likely benign (Jan 21, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001831895.1 First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021	Comment: This variant is associated with the following publications: (PMID: 26548919, 23772360)
Uncertain significance (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Microcephaly 7, primary, autosomal recessive Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001254501.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
Likely benign (Sep 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004032949.11 First in ClinVar: Sep 16, 2023 Last updated: Oct 20, 2024	Comment: STIL: BP4, BP5 Number of individuals with the variant: 11
not provided (-)	no classification provided Method: phenotyping only	Microcephaly 7, primary, autosomal recessive Affected status: unknown Allele origin: unknown	GenomeConnect - Brain Gene Registry Accession: SCV003931228.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023	Comment: Variant classified as Uncertain significance and reported on 12-06-2016 by Baylor Medical Genetics Laboratories. Assertions are reported exactly as they appear on the patient provided … (more) Variant classified as Uncertain significance and reported on 12-06-2016 by Baylor Medical Genetics Laboratories. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less) Clinical Features: Failure to thrive (present) Indication for testing: Diagnostic Age: 0-9 years Sex: female Method: Exome Sequencing Testing laboratory: Baylor Genetics Date variant was reported to submitter: 2016-12-06 Testing laboratory interpretation: Uncertain significance

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

Comment:

Variant classified as Uncertain significance and reported on 12-06-2016 by Baylor Medical Genetics Laboratories. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genetic causes of MCPH in consanguineous Pakistani families.	Kraemer N	Clinical genetics	2016	PMID: 26548919
In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ).	Kumar A	FEBS open bio	2012	PMID: 23772360
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=STIL	-	-	-	-

Text-mined citations for rs149185431 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001048166.1(STIL):c.1136C>T (p.Ser379Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs149185431 ...