NM_000190.4(HMBS):c.973C>T (p.Arg325Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 29, 2023
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:: RCV001382070.5

Allele description [Variation Report for NM_000190.4(HMBS):c.973C>T (p.Arg325Ter)]

NM_000190.4(HMBS):c.973C>T (p.Arg325Ter)

Gene:

HMBS:hydroxymethylbilane synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_000190.4(HMBS):c.973C>T (p.Arg325Ter)

HGVS:

NC_000011.10:g.119093170C>T
NG_008093.1:g.13294C>T
NM_000190.4:c.973C>TMANE SELECT
NM_001024382.2:c.922C>T
NM_001258208.2:c.853C>T
NM_001258209.2:c.802C>T
NP_000181.2:p.Arg325Ter
NP_001019553.1:p.Arg308Ter
NP_001245137.1:p.Arg285Ter
NP_001245138.1:p.Arg268Ter
LRG_1076t1:c.973C>T
LRG_1076t2:c.922C>T
LRG_1076:g.13294C>T
LRG_1076p1:p.Arg325Ter
LRG_1076p2:p.Arg308Ter
NC_000011.9:g.118963880C>T

Protein change:

R268*

Links:

dbSNP: rs2134885779

NCBI 1000 Genomes Browser:

rs2134885779

Molecular consequence:

NM_000190.4:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001024382.2:c.922C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258208.2:c.853C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258209.2:c.802C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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604983 (1)
OMIM
Mus musculus BAC clone RP23-322O24 from chromosome 7, complete sequence
Mus musculus BAC clone RP23-322O24 from chromosome 7, complete sequence
gi|117557636|gb|AC188457.2||gnl|wug 23-322O24

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001580690	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8565205, 18627369, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580690

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

R325X mutation in exon 15 of the hydroxymethylbilane synthase gene identified in two Danish families with acute intermittent porphyria.

Petersen NE, Nissen H, Hansen TS, Rasmussen K, Brock A, Hørder M.

Clin Chem. 1996 Jan;42(1):106-7. No abstract available.

PubMed [citation]

PMID:: 8565205

HMBS mutations in Chinese patients with acute intermittent porphyria.

Yang CC, Kuo HC, You HL, Wang J, Huang CC, Liu CY, Lan MY, Stephenson DA, Lee MJ.

Ann Hum Genet. 2008 Sep;72(Pt 5):683-6. doi: 10.1111/j.1469-1809.2008.00463.x.

PubMed [citation]

PMID:: 18627369

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580690.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg325*) in the HMBS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the HMBS protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with acute intermittent porphyria (PMID: 8565205, 18627369; Invitae). ClinVar contains an entry for this variant (Variation ID: 1070048). For these reasons, this variant has been classified as Pathogenic.

#	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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