NM_000190.4(HMBS):c.912+2T>C AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 11, 2021
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:: RCV001389656.7

Allele description [Variation Report for NM_000190.4(HMBS):c.912+2T>C]

NM_000190.4(HMBS):c.912+2T>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.912+2T>C

HGVS:

NC_000011.10:g.119093023T>C
NG_008093.1:g.13147T>C
NG_124182.1:g.376T>C
NM_000190.4:c.912+2T>CMANE SELECT
NM_001024382.2:c.861+2T>C
NM_001258208.2:c.792+2T>C
NM_001258209.2:c.741+2T>C
LRG_1076t1:c.912+2T>C
LRG_1076t2:c.861+2T>C
LRG_1076:g.13147T>C
NC_000011.9:g.118963733T>C

Links:

dbSNP: rs2134884322

NCBI 1000 Genomes Browser:

rs2134884322

Molecular consequence:

NM_000190.4:c.912+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001024382.2:c.861+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258208.2:c.792+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258209.2:c.741+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001591094	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 11, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17576681, 9536098, 31044425, 10453740, 8268934, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591094

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 11, 2021)

germline

clinical testing

PubMed (6)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591094.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with acute intermittent porphyria (PMID: 31044425, 10453740, 8268934, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in the last intron (intron 13) of the HMBS gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

#	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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