NM_000190.4(HMBS):c.652-1G>C AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 12, 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:: RCV001958670.4

Allele description [Variation Report for NM_000190.4(HMBS):c.652-1G>C]

NM_000190.4(HMBS):c.652-1G>C

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.652-1G>C

HGVS:

NC_000011.10:g.119092403G>C
NG_008093.1:g.12527G>C
NM_000190.4:c.652-1G>CMANE SELECT
NM_001024382.2:c.601-1G>C
NM_001258208.2:c.651+240G>C
NM_001258209.2:c.600+240G>C
LRG_1076t1:c.652-1G>C
LRG_1076t2:c.601-1G>C
LRG_1076:g.12527G>C
NC_000011.9:g.118963113G>C

Links:

dbSNP: rs2134878857

NCBI 1000 Genomes Browser:

rs2134878857

Molecular consequence:

NM_001258208.2:c.651+240G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258209.2:c.600+240G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000190.4:c.652-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001024382.2:c.601-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002235163	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 12, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9199558, 16199547, 7757070, 7962538, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235163

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 12, 2022)

germline

clinical testing

PubMed (5)
[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

Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.

Puy H, Deybach JC, Lamoril J, Robreau AM, Da Silva V, Gouya L, Grandchamp B, Nordmann Y.

Am J Hum Genet. 1997 Jun;60(6):1373-83.

PubMed [citation]

PMID:: 9199558
PMCID:: PMC1716106

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002235163.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as 652-1 cag>cac. Disruption of this splice site has been observed in individual(s) with acute intermittent porphyria (PMID: 9199558). This sequence change affects an acceptor splice site in intron 10 of the HMBS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HMBS are known to be pathogenic (PMID: 7757070, 7962538).

#	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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