NM_000142.5(FGFR3):c.1331C>T (p.Ser444Phe) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 15, 2023
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:: RCV003558537.2

Allele description [Variation Report for NM_000142.5(FGFR3):c.1331C>T (p.Ser444Phe)]

NM_000142.5(FGFR3):c.1331C>T (p.Ser444Phe)

Gene:

FGFR3:fibroblast growth factor receptor 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000142.5(FGFR3):c.1331C>T (p.Ser444Phe)

HGVS:

NC_000004.12:g.1804888C>T
NG_012632.1:g.16577C>T
NM_000142.5:c.1331C>TMANE SELECT
NM_001163213.2:c.1337C>T
NM_001354809.2:c.1334C>T
NM_001354810.2:c.1334C>T
NM_022965.4:c.995C>T
NP_000133.1:p.Ser444Phe
NP_000133.1:p.Ser444Phe
NP_001156685.1:p.Ser446Phe
NP_001341738.1:p.Ser445Phe
NP_001341739.1:p.Ser445Phe
NP_075254.1:p.Ser332Phe
LRG_1021t1:c.1331C>T
LRG_1021:g.16577C>T
LRG_1021p1:p.Ser444Phe
NC_000004.11:g.1806615C>T
NM_000142.4:c.1331C>T
NR_148971.2:n.1757C>T

Protein change:

S332F

Links:

dbSNP: rs761325047

NCBI 1000 Genomes Browser:

rs761325047

Molecular consequence:

NM_000142.5:c.1331C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001163213.2:c.1337C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354809.2:c.1334C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354810.2:c.1334C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022965.4:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_148971.2:n.1757C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004277522	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 15, 2023)	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

SCV004277522

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 15, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004277522.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR3 protein function. ClinVar contains an entry for this variant (Variation ID: 585087). This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. This variant is present in population databases (rs761325047, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 444 of the FGFR3 protein (p.Ser444Phe).

#	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: Sep 29, 2024

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Relating variation to medicine