VCV000984510.8 - ClinVar

NM_003665.4(FCN3):c.232+1G>A

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.

(4)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003665.4(FCN3):c.232+1G>A

Variation ID: 984510 Accession: VCV000984510.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p36.11 1: 27373964 (GRCh38) [ NCBI UCSC ] 1: 27700455 (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 12, 2020	Aug 26, 2023	Jul 28, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_003665.4:c.232+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_173452.3:c.232+1G>A		splice donor
NC_000001.11:g.27373964C>T
NC_000001.10:g.27700455C>T
NG_016279.1:g.5861G>A
LRG_171:g.5861G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000001.11:27373963:C:T

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.

0.00080 (T)

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

1000 Genomes Project 0.00080

1000 Genomes Project 30x 0.00094

The Genome Aggregation Database (gnomAD), exomes 0.00144

The Genome Aggregation Database (gnomAD) 0.00153

Exome Aggregation Consortium (ExAC) 0.00158

Trans-Omics for Precision Medicine (TOPMed) 0.00173

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00208

Links

dbSNP: rs141300199 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.
FCN3		-	-	GRCh38 GRCh37	41	51

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 specified	Uncertain significance (1)	criteria provided, single submitter	Jul 28, 2023	RCV001264582.4
not provided	Uncertain significance (2)	no assertion criteria provided	-	RCV001729829.4
Immunodeficiency due to ficolin3 deficiency	Uncertain significance (1)	criteria provided, single submitter	Mar 28, 2022	RCV002504380.3

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.
Uncertain significance (Mar 28, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Immunodeficiency due to ficolin3 deficiency Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002814561.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Jul 28, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001442808.2 First in ClinVar: Nov 12, 2020 Last updated: Aug 26, 2023	Comment: Variant summary: FCN3 c.232+1G>A is located in a canonical splice-site in intron 3 and is predicted to affect mRNA splicing resulting in a significantly altered … (more) Variant summary: FCN3 c.232+1G>A is located in a canonical splice-site in intron 3 and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. Sequence alignment suggests that this variant is not conserved through vertebrate species. In addition, the isoform lacking the exon 4 is found with low expression level in normal tissues (GTExPortal), suggesting missing exon 4 may not be disease-causing. The variant allele was found at a frequency of 0.0014 in 250554 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.232+1G>A in individuals affected with Immunodeficiency Due To Ficolin 3 Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
Uncertain significance (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001978049.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021
Uncertain significance (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001980576.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021

Comment:

Variant summary: FCN3 c.232+1G>A is located in a canonical splice-site in intron 3 and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. Sequence alignment suggests that this variant is not conserved through vertebrate species. In addition, the isoform lacking the exon 4 is found with low expression level in normal tissues (GTExPortal), suggesting missing exon 4 may not be disease-causing. The variant allele was found at a frequency of 0.0014 in 250554 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.232+1G>A in individuals affected with Immunodeficiency Due To Ficolin 3 Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs141300199 ...

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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_003665.4(FCN3):c.232+1G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs141300199 ...