NM_001061.7(TBXAS1):c.1235G>A (p.Arg412Gln) AND Ghosal hematodiaphyseal syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 6, 2020
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:: RCV000012664.28

Allele description [Variation Report for NM_001061.7(TBXAS1):c.1235G>A (p.Arg412Gln)]

NM_001061.7(TBXAS1):c.1235G>A (p.Arg412Gln)

Gene:

TBXAS1:thromboxane A synthase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_001061.7(TBXAS1):c.1235G>A (p.Arg412Gln)

Other names:

R413E

HGVS:

NC_000007.14:g.140015731G>A
NG_008422.2:g.242350G>A
NM_001061.7:c.1235G>AMANE SELECT
NM_001130966.5:c.1235G>A
NM_001166253.4:c.1373G>A
NM_001166254.4:c.1034G>A
NM_001314028.4:c.1178G>A
NM_001366537.3:c.1052G>A
NM_030984.6:c.1235G>A
NP_001052.3:p.Arg412Gln
NP_001124438.2:p.Arg412Gln
NP_001159725.2:p.Arg458Gln
NP_001159726.1:p.Arg345Gln
NP_001300957.1:p.Arg393Gln
NP_001353466.1:p.Arg351Gln
NP_112246.3:p.Arg412Gln
LRG_579t4:c.1376G>A
LRG_579:g.242350G>A
NC_000007.13:g.139715531G>A
NM_001061.4:c.1238G>A
NM_001166253.1:c.1376G>A
NM_001166253.3:c.1373G>A

Protein change:

R345Q; ARG413GLU

Links:

OMIM: 274180.0004; dbSNP: rs199422117

NCBI 1000 Genomes Browser:

rs199422117

Molecular consequence:

NM_001061.7:c.1235G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130966.5:c.1235G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166253.4:c.1373G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166254.4:c.1034G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001314028.4:c.1178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001366537.3:c.1052G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_030984.6:c.1235G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ghosal hematodiaphyseal syndrome
Identifiers:: MedGen: C4016444

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000032899	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001142376	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Uncertain significance (Jan 6, 2020)	germline	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000032899

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2008)

germline

literature only

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

SCV001142376

Reproductive Health Research and Development, BGI Genomics

no assertion criteria provided

Uncertain significance
(Jan 6, 2020)

germline

curation

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	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome).

Geneviève D, Proulle V, Isidor B, Bellais S, Serre V, Djouadi F, Picard C, Vignon-Savoye C, Bader-Meunier B, Blanche S, de Vernejoul MC, Legeai-Mallet L, Fischer AM, Le Merrer M, Dreyfus M, Gaussem P, Munnich A, Cormier-Daire V.

Nat Genet. 2008 Mar;40(3):284-6. doi: 10.1038/ng.2007.66. Epub 2008 Feb 10.

PubMed [citation]

PMID:: 18264100

Details of each submission

From OMIM, SCV000032899.2

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

Description

In affected members of a consanguineous Pakistani family with Ghosal hematodiaphyseal syndrome (GHDD; 231095), Genevieve et al. (2008) detected homozygosity for a 1238G-A transition in the TBXAS1 gene that resulted in an arg413-to-glu amino acid substitution (R413E).

#	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

From Reproductive Health Research and Development, BGI Genomics, SCV001142376.1

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

Description

NM_001061.4:c.1238G>A in the TBXAS1 gene has an allele frequency of 0.007 in South Asian subpopulation in the gnomAD database. It has been detected in homozygous state in one consanguineous family with Ghosal hematodiaphyseal dysplasia syndrome (PMID: 18264100). We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PP4.

#	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: May 12, 2024

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