NM_000190.4(HMBS):c.210_210+5delinsT AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 1, 2019
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:: RCV001243098.4

Allele description

NM_000190.4(HMBS):c.210_210+5delinsT

Gene:

HMBS:hydroxymethylbilane synthase [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_000190.4(HMBS):c.210_210+5delinsT

HGVS:

NC_000011.10:g.119089131_119089136delGGTAACinsT
NC_000011.10:g.119089131_119089136delinsT
NG_008093.1:g.9255_9260delinsT
NM_000190.4:c.210_210+5delinsTMANE SELECT
NM_001024382.2:c.159_159+5delinsT
NM_001258208.2:c.210_210+5delinsT
NM_001258209.2:c.159_159+5delinsT
LRG_1076t1:c.210_210+5delinsT
LRG_1076t2:c.159_159+5delinsT
LRG_1076:g.9255_9260delinsT
NC_000011.9:g.118959841_118959846delinsT
NC_000011.9:g.118959841_118959846delinsT
NM_000190.3:c.210_210+5delinsT

Links:

dbSNP: rs1946169082

NCBI 1000 Genomes Browser:

rs1946169082

Molecular consequence:

NM_000190.4:c.210_210+5delinsT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001024382.2:c.159_159+5delinsT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258208.2:c.210_210+5delinsT - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258209.2:c.159_159+5delinsT - 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
SCV001416232	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 1, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 7757070, 7962538, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001416232

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 1, 2019)

germline

clinical testing

PubMed (4)
[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

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

Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene.

Kauppinen R, Mustajoki S, Pihlaja H, Peltonen L, Mustajoki P.

Hum Mol Genet. 1995 Feb;4(2):215-22.

PubMed [citation]

PMID:: 7757070

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001416232.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants 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). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has been observed in an individual affected with¬†acute intermittent porphyria¬†(Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 4 of the HMBS gene. It is expected to disrupt RNA splicing and likely results in an absent or 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 1, 2024

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