NM_000190.4(HMBS):c.887dup (p.Ala297fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 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:: RCV003557678.2

Allele description [Variation Report for NM_000190.4(HMBS):c.887dup (p.Ala297fs)]

NM_000190.4(HMBS):c.887dup (p.Ala297fs)

Gene:

HMBS:hydroxymethylbilane synthase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_000190.4(HMBS):c.887dup (p.Ala297fs)

HGVS:

NC_000011.10:g.119092996dup
NG_008093.1:g.13120dup
NG_124182.1:g.349dup
NM_000190.4:c.887dupMANE SELECT
NM_001024382.2:c.836dup
NM_001258208.2:c.767dup
NM_001258209.2:c.716dup
NM_001425052.1:c.836dup
NM_001425053.1:c.836dup
NM_001425054.1:c.836dup
NM_001425056.1:c.878dup
NM_001425057.1:c.869dup
NM_001425058.1:c.848dup
NM_001425059.1:c.833dup
NM_001425061.1:c.728dup
NM_001425062.1:c.722dup
NM_001425063.1:c.722dup
NM_001425065.1:c.713dup
NP_000181.2:p.Ala297fs
NP_001019553.1:p.Ala280fs
NP_001245137.1:p.Ala257fs
NP_001245138.1:p.Ala240fs
NP_001411981.1:p.Ala280Glyfs
NP_001411982.1:p.Ala280Glyfs
NP_001411983.1:p.Ala280Glyfs
NP_001411985.1:p.Ala294Glyfs
NP_001411986.1:p.Ala291Glyfs
NP_001411987.1:p.Ala284Glyfs
NP_001411988.1:p.Ala279Glyfs
NP_001411990.1:p.Ala244Glyfs
NP_001411991.1:p.Ala242Glyfs
NP_001411992.1:p.Ala242Glyfs
NP_001411994.1:p.Ala239Glyfs
LRG_1076t1:c.887dup
LRG_1076t2:c.836dup
LRG_1076:g.13120dup
LRG_1076p1:p.Ala297fs
LRG_1076p2:p.Ala280fs
NC_000011.9:g.118963705_118963706insA
NC_000011.9:g.118963706dup

Protein change:

A240fs

Molecular consequence:

NM_000190.4:c.887dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001024382.2:c.836dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258208.2:c.767dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258209.2:c.716dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425052.1:c.836dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425053.1:c.836dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425054.1:c.836dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425056.1:c.878dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425057.1:c.869dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425058.1:c.848dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425059.1:c.833dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425061.1:c.728dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425062.1:c.722dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425063.1:c.722dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001425065.1:c.713dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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cytochrome P450 307a1, partial [Exorista sorbillans]
cytochrome P450 307a1, partial [Exorista sorbillans]
gi|2664562893|gb|WVH45124.1|

Protein
phosphatidylinositol 4-kinase type 2-beta, partial [Vicugna pacos]
phosphatidylinositol 4-kinase type 2-beta, partial [Vicugna pacos]
gi|970721968|ref|XP_015097007.1|

Protein
cohesin subunit SA-2 isoform b [Homo sapiens]
cohesin subunit SA-2 isoform b [Homo sapiens]
gi|112789530|ref|NP_001036216.1|

Protein
Papio ursinus
Papio ursinus
Papio ursinus genome sequencing project.

BioProject
Mdh1 [Ostrinia nubilalis]
Mdh1 [Ostrinia nubilalis]
Gene ID:135072675

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004294976	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8168829, 20536026, 31044425, 10657149, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294976

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 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

Acute intermittent porphyria caused by a single base insertion of C in exon 15 of the porphobilinogen deaminase gene that results in a frame shift and premature stopping of translation.

Daimon M, Yamatani K, Igarashi M, Fukase N, Morita Y, Ogawa A, Tominaga M, Sasaki H.

Hum Genet. 1994 May;93(5):533-7.

PubMed [citation]

PMID:: 8168829

[Molecular genetic study of acute intermittent porphyria in Russia: mutation analysis and functional polymorphism search in porphobilinogen deaminase gene].

Surin VL, Luchinina IuA, Selivanova DS, Pustovoĭt IaS, Karpova IS, Pivnik AV, Luk'ianenko AV, Kravchenko SK.

Genetika. 2010 Apr;46(4):540-52. Russian.

PubMed [citation]

PMID:: 20536026

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004294976.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the HMBS protein in which other variant(s) (p.Leu341Cysfs*3) have been determined to be pathogenic (PMID: 8168829, 20536026, 31044425; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant is also known as ins886 A. This premature translational stop signal has been observed in individual(s) with clinical features of acute intermittent porphyria (PMID: 10657149). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala297Glyfs*10) in the HMBS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 65 amino acid(s) of the HMBS protein.

#	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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