NM_006892.4(DNMT3B):c.710C>G (p.Ser237Cys) AND Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 2022
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:: RCV001210853.8

Allele description [Variation Report for NM_006892.4(DNMT3B):c.710C>G (p.Ser237Cys)]

NM_006892.4(DNMT3B):c.710C>G (p.Ser237Cys)

Gene:

DNMT3B:DNA methyltransferase 3 beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.21

Genomic location:

Preferred name:

NM_006892.4(DNMT3B):c.710C>G (p.Ser237Cys)

HGVS:

NC_000020.11:g.32788909C>G
NG_007290.1:g.31525C>G
NM_001207055.2:c.584C>G
NM_001207056.2:c.482C>G
NM_006892.4:c.710C>GMANE SELECT
NM_175848.2:c.710C>G
NM_175849.2:c.710C>G
NM_175850.3:c.746C>G
NP_001193984.1:p.Ser195Cys
NP_001193985.1:p.Ser161Cys
NP_008823.1:p.Ser237Cys
NP_787044.1:p.Ser237Cys
NP_787045.1:p.Ser237Cys
NP_787046.1:p.Ser249Cys
LRG_56t1:c.710C>G
LRG_56:g.31525C>G
NC_000020.10:g.31376715C>G
NM_006892.3:c.710C>G

Protein change:

S161C

Links:

dbSNP: rs964977606

NCBI 1000 Genomes Browser:

rs964977606

Molecular consequence:

NM_001207055.2:c.584C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001207056.2:c.482C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006892.4:c.710C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_175848.2:c.710C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_175849.2:c.710C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_175850.3:c.746C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency (ICF1)
Synonyms:: ICF syndrome; Immunodeficiency syndrome, variable; Centromeric instability, immunodeficiency syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0000133; MedGen: C0398788; OMIM: PS242860

Recent activity

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Mus musculus sorbin and SH3 domain containing 3 (Sorbs3), transcript variant 2, ...
Mus musculus sorbin and SH3 domain containing 3 (Sorbs3), transcript variant 2, mRNA
gi|2587328251|ref|NM_001271407.2|

Nucleotide
Oncostatin M Receptor beta Subunit
Oncostatin M Receptor beta Subunit
An ONCOSTATIN M-specific receptor subunit that combines with CYTOKINE RECEPTOR GP130 to form the ONCOSTATIN M TYPE II RECEPTOR.<br/>Year introduced: 2007(2003)

MeSH
Receptors, OSM-LIF
Receptors, OSM-LIF
Cell surface receptors formed from the dimerization of LIF RECEPTOR ALPHA SUBUNIT with CYTOKINE RECEPTOR GP130. Although originally described as receptors for LEUKEMIA INHIBIT...<br/>Year introduced: 2007(1991)

MeSH
Heterogeneous-Nuclear Ribonucleoprotein Group M
Heterogeneous-Nuclear Ribonucleoprotein Group M
A group of closely-related 72-74-kDa heterogeneous-nuclear ribonucleoproteins that are involved in RNA SPLICING events.<br/>Year introduced: 2003

MeSH
Apolipoproteins M
Apolipoproteins M
Apolipoproteins and lipocalins that occur in HIGH-DENSITY LIPOPROTEINS. They bind or transport lipids in the blood including sphingosine-1-phosphate, MYRISTIC ACID; STEARIC AC...<br/>Year introduced: 2018

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001382361	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 2022)	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

SCV001382361

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 2022)

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, SCV001382361.5

#	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) performed at Invitae indicates that this missense variant is not expected to disrupt DNMT3B protein function. ClinVar contains an entry for this variant (Variation ID: 941131). This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 237 of the DNMT3B protein (p.Ser237Cys).

#	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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