NM_000190.4(HMBS):c.940_941del (p.Gln314fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 3, 2023
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:: RCV001229602.7

Allele description [Variation Report for NM_000190.4(HMBS):c.940_941del (p.Gln314fs)]

NM_000190.4(HMBS):c.940_941del (p.Gln314fs)

Gene:

HMBS:hydroxymethylbilane synthase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_000190.4(HMBS):c.940_941del (p.Gln314fs)

Other names:

p.Gln314Valfs*8

HGVS:

NC_000011.10:g.119093135CA[1]
NG_008093.1:g.13259CA[1]
NM_000190.4:c.940_941delMANE SELECT
NM_001024382.2:c.889_890del
NM_001258208.2:c.820_821del
NM_001258209.2:c.769_770del
NP_000181.2:p.Gln314fs
NP_001019553.1:p.Gln297fs
NP_001245137.1:p.Gln274fs
NP_001245138.1:p.Gln257fs
LRG_1076t1:c.940_941del
LRG_1076t2:c.889_890del
LRG_1076:g.13259CA[1]
LRG_1076p1:p.Gln314fs
LRG_1076p2:p.Gln297fs
NC_000011.9:g.118963845CA[1]
NC_000011.9:g.118963845_118963846del
NM_000190.3:c.940_941del

Protein change:

Q257fs

Links:

dbSNP: rs1407093112

NCBI 1000 Genomes Browser:

rs1407093112

Molecular consequence:

NM_000190.4:c.940_941del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001024382.2:c.889_890del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258208.2:c.820_821del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258209.2:c.769_770del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV001402053	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 9, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10944860, 19138865, 30740734, 28492532
SCV004226629	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30740734, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001402053

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 9, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004226629

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 3, 2023)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two deletion mutations in the hydroxymethylbilane synthase gene in two unrelated Japanese patients with acute intermittent porphyria.

Maeda N, Horie Y, Adachi K, Nanba E, Kawasaki H, Daimon M, Kudo Y, Kondo M.

J Hum Genet. 2000;45(4):263-8.

PubMed [citation]

PMID:: 10944860

Correlation between biochemical findings, structural and enzymatic abnormalities in mutated HMBS identified in six Israeli families with acute intermittent porphyria.

Ulbrichova D, Schneider-Yin X, Mamet R, Saudek V, Martasek P, Minder EI, Schoenfeld N.

Blood Cells Mol Dis. 2009 Mar-Apr;42(2):167-73. doi: 10.1016/j.bcmd.2008.11.001. Epub 2009 Jan 12.

PubMed [citation]

PMID:: 19138865

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001402053.5

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

Description

This variant is present in population databases (no rsID available, gnomAD 0.003%). 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.Gln328Valfs*30) have been determined to be pathogenic (PMID: 10944860, 19138865). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 956739). This premature translational stop signal has been observed in individuals with AIP (PMID: 30740734; Invitae). This sequence change creates a premature translational stop signal (p.Gln314Valfs*8) in the HMBS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226629.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

PP4, PM2, PVS1_strong

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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