NM_001370298.3(FGD4):c.984G>T (p.Glu328Asp) AND Charcot-Marie-Tooth disease type 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 21, 2021
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:: RCV001041763.7

Allele description [Variation Report for NM_001370298.3(FGD4):c.984G>T (p.Glu328Asp)]

NM_001370298.3(FGD4):c.984G>T (p.Glu328Asp)

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.984G>T (p.Glu328Asp)

HGVS:

NC_000012.12:g.32582440G>T
NG_008626.2:g.187912G>T
NM_001304481.2:c.828G>T
NM_001304483.2:c.-272G>T
NM_001304484.2:c.-579G>T
NM_001330373.2:c.294G>T
NM_001330374.2:c.294G>T
NM_001370297.1:c.49-16057G>T
NM_001370298.3:c.984G>TMANE SELECT
NM_001384126.1:c.984G>T
NM_001384127.1:c.573G>T
NM_001384128.1:c.573G>T
NM_001384130.1:c.294G>T
NM_001384131.1:c.573G>T
NM_001384132.1:c.573G>T
NM_001385118.1:c.573G>T
NM_139241.3:c.573G>T
NP_001291410.1:p.Glu276Asp
NP_001291410.1:p.Glu276Asp
NP_001317302.1:p.Glu98Asp
NP_001317303.1:p.Glu98Asp
NP_001357227.2:p.Glu328Asp
NP_001371055.1:p.Glu328Asp
NP_001371056.1:p.Glu191Asp
NP_001371057.1:p.Glu191Asp
NP_001371059.1:p.Glu98Asp
NP_001371060.1:p.Glu191Asp
NP_001371061.1:p.Glu191Asp
NP_001372047.1:p.Glu191Asp
NP_640334.2:p.Glu191Asp
LRG_240t1:c.573G>T
LRG_240t2:c.828G>T
LRG_240:g.187912G>T
LRG_240p1:p.Glu191Asp
LRG_240p2:p.Glu276Asp
NC_000012.11:g.32735374G>T
NM_001304481.1:c.828G>T
NR_168884.1:n.810G>T

Protein change:

E191D

Links:

dbSNP: rs1487363420

NCBI 1000 Genomes Browser:

rs1487363420

Molecular consequence:

NM_001304483.2:c.-272G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001304484.2:c.-579G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001370297.1:c.49-16057G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001304481.2:c.828G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330373.2:c.294G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330374.2:c.294G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370298.3:c.984G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384126.1:c.984G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384127.1:c.573G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384128.1:c.573G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384130.1:c.294G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384131.1:c.573G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384132.1:c.573G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385118.1:c.573G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139241.3:c.573G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_168884.1:n.810G>T - 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
SCV001205398	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 21, 2021)	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

SCV001205398

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 21, 2021)

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, SCV001205398.5

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

Description

This variant has not been reported in the literature in individuals with FGD4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 191 of the FGD4 protein (p.Glu191Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. 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 aspartic acid 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. 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.

#	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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