VCV000255321.53 - ClinVar

NM_000142.5(FGFR3):c.1014C>T (p.Thr338=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

7 out of 11 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000142.5(FGFR3):c.1014C>T (p.Thr338=)

Variation ID: 255321 Accession: VCV000255321.53

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4p16.3 4: 1803775 (GRCh38) [ NCBI UCSC ] 4: 1805502 (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	Oct 3, 2016	Jul 13, 2025	May 1, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000142.5:c.1014C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000133.1:p.Thr338=	synonymous
NM_001163213.2:c.1082-555C>T		intron variant
NM_001354809.2:c.1014C>T	NP_001341738.1:p.Thr338=	synonymous
NM_001354810.2:c.1014C>T	NP_001341739.1:p.Thr338=	synonymous
NM_022965.4:c.931-1049C>T		intron variant
NR_148971.2:n.1440C>T		non-coding transcript variant
NC_000004.12:g.1803775C>T
NC_000004.11:g.1805502C>T
NG_012632.1:g.15464C>T
LRG_1021:g.15464C>T
LRG_1021t1:c.1014C>T	LRG_1021p1:p.Thr338=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000004.12:1803774: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.

0.00160 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00458

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00523

1000 Genomes Project 30x 0.00141

1000 Genomes Project 0.00160

Trans-Omics for Precision Medicine (TOPMed) 0.00322

The Genome Aggregation Database (gnomAD) 0.00328

Exome Aggregation Consortium (ExAC) 0.00399

The Genome Aggregation Database (gnomAD), exomes 0.00456

Links

ClinGen: CA2810164 dbSNP: rs4647928 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.
FGFR3		No evidence available	No evidence available	GRCh38 GRCh37	1104	1257

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	Benign (4)	criteria provided, multiple submitters, no conflicts	Apr 25, 2017	RCV000247535.20
not provided	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	May 1, 2025	RCV001579445.47

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.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000302606.1 First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016

Benign (Apr 25, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000729010.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005263657.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024

Benign (Jul 13, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000332472.5 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FGFR3 Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed

Benign (Jan 27, 2025) C Contributing to aggregate classification	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: SCV000762849.7 First in ClinVar: May 28, 2018 Last updated: Feb 25, 2025

Benign (May 23, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001477634.2 First in ClinVar: Jan 26, 2021 Last updated: Mar 11, 2025

Likely benign (May 01, 2025) C Contributing to aggregate classification	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: SCV001962550.26 First in ClinVar: Oct 08, 2021 Last updated: Jul 13, 2025	Comment: FGFR3: BP4, BP7, BS2 Number of individuals with the variant: 8

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001800670.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001807263.1 First in ClinVar: Aug 26, 2021 Last updated: Aug 26, 2021

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001951124.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021

Likely benign (-) N Not contributing to aggregate classification	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: SCV001975768.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021

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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FGFR3	-	-	-	-

Text-mined citations for rs4647928 ...

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 Jul 13, 2025

ClinVar Genomic variation as it relates to human health

NM_000142.5(FGFR3):c.1014C>T (p.Thr338=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs4647928 ...