NM_024589.3(ROGDI):c.691A>G (p.Met231Val) AND Amelocerebrohypohidrotic syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 7, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001056123.5

Allele description [Variation Report for NM_024589.3(ROGDI):c.691A>G (p.Met231Val)]

NM_024589.3(ROGDI):c.691A>G (p.Met231Val)

Gene:

ROGDI:rogdi atypical leucine zipper [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_024589.3(ROGDI):c.691A>G (p.Met231Val)

HGVS:

NC_000016.10:g.4797942T>C
NG_032174.1:g.10009A>G
NM_024589.1:c.691A>G
NM_024589.3:c.691A>GMANE SELECT
NP_078865.1:p.Met231Val
LRG_455t1:c.691A>G
LRG_455:g.10009A>G
NC_000016.9:g.4847943T>C
NM_024589.2:c.691A>G
NR_046480.2:n.698A>G

Protein change:

M231V

Links:

dbSNP: rs137934107

NCBI 1000 Genomes Browser:

rs137934107

Molecular consequence:

NM_024589.3:c.691A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_046480.2:n.698A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Amelocerebrohypohidrotic syndrome (KTZS)
Synonyms:: EPILEPSY, DEMENTIA, AND AMELOGENESIS IMPERFECTA; Kohlschutter Tonz syndrome; Epilepsy dementia amelogenesis imperfecta; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009185; MedGen: C0406740; Orphanet: 1946; OMIM: 226750

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001220544	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 7, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002506834	New York Genome Center - CSER-NYCKidSeq	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Uncertain significance (May 27, 2021)	inherited	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001220544

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 7, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002506834

New York Genome Center - CSER-NYCKidSeq

criteria provided, single submitter

(NYGC Assertion Criteria 2020)

Uncertain significance
(May 27, 2021)

inherited

clinical testing

Citation Link

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
not provided	inherited	unknown	1	not provided	not provided	1	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, SCV001220544.4

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 231 of the ROGDI protein (p.Met231Val). This variant is present in population databases (rs137934107, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ROGDI-related conditions. ClinVar contains an entry for this variant (Variation ID: 851681). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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

From New York Genome Center - CSER-NYCKidSeq, SCV002506834.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine