NM_003839.4(TNFRSF11A):c.508A>G (p.Arg170Gly) AND Autosomal recessive osteopetrosis 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 26, 2009
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000006681.3

Allele description [Variation Report for NM_003839.4(TNFRSF11A):c.508A>G (p.Arg170Gly)]

NM_003839.4(TNFRSF11A):c.508A>G (p.Arg170Gly)

Gene:

TNFRSF11A:TNF receptor superfamily member 11a [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.33

Genomic location:

Preferred name:

NM_003839.4(TNFRSF11A):c.508A>G (p.Arg170Gly)

HGVS:

NC_000018.10:g.62358328A>G
NG_008098.1:g.38014A>G
NM_001270949.2:c.508A>G
NM_001270950.2:c.508A>G
NM_001270951.2:c.508A>G
NM_001278268.2:c.466A>G
NM_003839.4:c.508A>GMANE SELECT
NP_001257878.1:p.Arg170Gly
NP_001257879.1:p.Arg170Gly
NP_001257880.1:p.Arg170Gly
NP_001265197.1:p.Arg156Gly
NP_003830.1:p.Arg170Gly
LRG_194:g.38014A>G
NC_000018.9:g.60025561A>G
Q9Y6Q6:p.Arg170Gly

Protein change:

R156G; ARG170GLY

Links:

UniProtKB: Q9Y6Q6#VAR_046791; OMIM: 603499.0003; dbSNP: rs121908655

NCBI 1000 Genomes Browser:

rs121908655

Molecular consequence:

NM_001270949.2:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270950.2:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270951.2:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278268.2:c.466A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003839.4:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive osteopetrosis 7
Synonyms:: Osteopetrosis osteoclast-poor with hypogammaglobulinemia; Autosomal recessive osteoclast-poor osteopetrosis with hypogammaglobulinemia
Identifiers:: MONDO: MONDO:0012859; MedGen: C2676766; Orphanet: 178389; OMIM: 612301

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026864	OMIM	no assertion criteria provided	Pathogenic (Nov 26, 2009)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 18606301, 19940926

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000026864

OMIM

no assertion criteria provided

Pathogenic
(Nov 26, 2009)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations.

Guerrini MM, Sobacchi C, Cassani B, Abinun M, Kilic SS, Pangrazio A, Moratto D, Mazzolari E, Clayton-Smith J, Orchard P, Coxon FP, Helfrich MH, Crockett JC, Mellis D, Vellodi A, Tezcan I, Notarangelo LD, Rogers MJ, Vezzoni P, Villa A, Frattini A.

Am J Hum Genet. 2008 Jul;83(1):64-76. doi: 10.1016/j.ajhg.2008.06.015.

PubMed [citation]

PMID:: 18606301
PMCID:: PMC2443850

Central control of fever and female body temperature by RANKL/RANK.

Hanada R, Leibbrandt A, Hanada T, Kitaoka S, Furuyashiki T, Fujihara H, Trichereau J, Paolino M, Qadri F, Plehm R, Klaere S, Komnenovic V, Mimata H, Yoshimatsu H, Takahashi N, von Haeseler A, Bader M, Kilic SS, Ueta Y, Pifl C, Narumiya S, Penninger JM.

Nature. 2009 Nov 26;462(7272):505-9. doi: 10.1038/nature08596.

PubMed [citation]

PMID:: 19940926

Details of each submission

From OMIM, SCV000026864.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a sister and brother, born of consanguineous Turkish parents, who had osteoclast-poor osteopetrosis and hypogammaglobulinemia (OPTB7; 612301) and were negative for mutations in known osteopetrosis genes, Guerrini et al. (2008) identified homozygosity for a 508A-G transition in the TNFRSF11A gene, resulting in an arg170-to-gly (R170G) substitution in an extracellular cysteine-rich region. The sibs' monocytes failed to differentiate in vitro into osteoclasts upon exposure to MCSF (CSF1; 120420) and RANKL (602642), in keeping with an osteoclast-intrinsic defect, and immunologic analysis showed that their hypogammaglobulinemia was associated with impairment in immunoglobulin-secreting B cells. The parents and 3 other unaffected relatives were heterozygous for the mutation, which was not found in more than 100 chromosomes from unrelated controls from the same geographic area. Hanada et al. (2009) demonstrated that these 2 children had a markedly abrogated fever response to severe pneumonia, confirmed by serology and chest x-ray.

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

Last Updated: Apr 23, 2022

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