NM_000190.4(HMBS):c.754G>A (p.Ala252Thr) AND Acute intermittent porphyria

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 26, 2024
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:: RCV000001537.13

Allele description [Variation Report for NM_000190.4(HMBS):c.754G>A (p.Ala252Thr)]

NM_000190.4(HMBS):c.754G>A (p.Ala252Thr)

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.754G>A (p.Ala252Thr)

HGVS:

NC_000011.10:g.119092506G>A
NG_008093.1:g.12630G>A
NM_000190.4:c.754G>AMANE SELECT
NM_001024382.2:c.703G>A
NM_001258208.2:c.652-252G>A
NM_001258209.2:c.601-252G>A
NP_000181.2:p.Ala252Thr
NP_001019553.1:p.Ala235Thr
LRG_1076t1:c.754G>A
LRG_1076t2:c.703G>A
LRG_1076:g.12630G>A
LRG_1076p1:p.Ala252Thr
LRG_1076p2:p.Ala235Thr
NC_000011.9:g.118963216G>A
NM_000190.3:c.754G>A
P08397:p.Ala252Thr

Protein change:

A235T; ALA252THR

Links:

UniProtKB: P08397#VAR_003667; OMIM: 609806.0032; dbSNP: rs118204113

NCBI 1000 Genomes Browser:

rs118204113

Molecular consequence:

NM_001258208.2:c.652-252G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001258209.2:c.601-252G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000190.4:c.754G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001024382.2:c.703G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Acute intermittent porphyria (AIP)
Synonyms:: Porphobilinogen deaminase deficiency; Uroporphyrinogen synthase deficiency; UPS deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008294; MedGen: C0162565; Orphanet: 79276; OMIM: 176000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021692	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001265198	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004807413	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 26, 2024)	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

SCV000021692

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 1993)

germline

literature only

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

SCV001265198

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV004807413

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 26, 2024)

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria.

Mgone CS, Lanyon WG, Moore MR, Louie GV, Connor JM.

Hum Genet. 1993 Dec;92(6):619-22.

PubMed [citation]

PMID:: 8262523

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000021692.5

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

Description

In a patient with acute intermittent porphyria (AIP; 176000), Mgone et al. (1993) identified a c.754G-A transition in exon 12 of the HMBS gene, resulting in an ala252-to-thr (A252T) substitution.

#	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 Illumina Laboratory Services, Illumina, SCV001265198.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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 Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004807413.1

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

#	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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