NM_001370298.3(FGD4):c.838A>G (p.Thr280Ala) AND Charcot-Marie-Tooth disease type 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 24, 2019
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:: RCV001217059.8

Allele description [Variation Report for NM_001370298.3(FGD4):c.838A>G (p.Thr280Ala)]

NM_001370298.3(FGD4):c.838A>G (p.Thr280Ala)

Gene:

FGD4:FYVE, RhoGEF and PH domain containing 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p11.21

Genomic location:

Preferred name:

NM_001370298.3(FGD4):c.838A>G (p.Thr280Ala)

HGVS:

NC_000012.12:g.32582294A>G
NG_008626.2:g.187766A>G
NM_001304481.2:c.682A>G
NM_001304483.2:c.-418A>G
NM_001304484.2:c.-725A>G
NM_001330373.2:c.148A>G
NM_001330374.2:c.148A>G
NM_001370297.1:c.49-16203A>G
NM_001370298.3:c.838A>GMANE SELECT
NM_001384126.1:c.838A>G
NM_001384127.1:c.427A>G
NM_001384128.1:c.427A>G
NM_001384130.1:c.148A>G
NM_001384131.1:c.427A>G
NM_001384132.1:c.427A>G
NM_001385118.1:c.427A>G
NM_139241.3:c.427A>G
NP_001291410.1:p.Thr228Ala
NP_001291410.1:p.Thr228Ala
NP_001317302.1:p.Thr50Ala
NP_001317303.1:p.Thr50Ala
NP_001357227.2:p.Thr280Ala
NP_001371055.1:p.Thr280Ala
NP_001371056.1:p.Thr143Ala
NP_001371057.1:p.Thr143Ala
NP_001371059.1:p.Thr50Ala
NP_001371060.1:p.Thr143Ala
NP_001371061.1:p.Thr143Ala
NP_001372047.1:p.Thr143Ala
NP_640334.2:p.Thr143Ala
LRG_240t1:c.427A>G
LRG_240t2:c.682A>G
LRG_240:g.187766A>G
LRG_240p1:p.Thr143Ala
LRG_240p2:p.Thr228Ala
NC_000012.11:g.32735228A>G
NM_001304481.1:c.682A>G
NR_168884.1:n.664A>G

Protein change:

T143A

Links:

dbSNP: rs1463004734

NCBI 1000 Genomes Browser:

rs1463004734

Molecular consequence:

NM_001304483.2:c.-418A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001304484.2:c.-725A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001370297.1:c.49-16203A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001304481.2:c.682A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330373.2:c.148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330374.2:c.148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370298.3:c.838A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384126.1:c.838A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384127.1:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384128.1:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384130.1:c.148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384131.1:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384132.1:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001385118.1:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_139241.3:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_168884.1:n.664A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4
Synonyms:: Charcot-Marie-Tooth, Type 4
Identifiers:: MONDO: MONDO:0018995; MedGen: C4082197

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001388886	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 24, 2019)	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

SCV001388886

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 24, 2019)

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, SCV001388886.5

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

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 143 of the FGD4 protein (p.Thr143Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant has not been reported in the literature in individuals with FGD4-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.

#	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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