NM_000190.4(HMBS):c.76C>T (p.Arg26Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 6, 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:: RCV000799514.14

Allele description [Variation Report for NM_000190.4(HMBS):c.76C>T (p.Arg26Cys)]

NM_000190.4(HMBS):c.76C>T (p.Arg26Cys)

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.76C>T (p.Arg26Cys)

Other names:

p.Arg26Cys

HGVS:

NC_000011.10:g.119088297C>T
NG_008093.1:g.8421C>T
NM_000190.4:c.76C>TMANE SELECT
NM_001024382.2:c.25C>T
NM_001258208.2:c.76C>T
NM_001258209.2:c.25C>T
NP_000181.2:p.Arg26Cys
NP_001019553.1:p.Arg9Cys
NP_001245137.1:p.Arg26Cys
NP_001245138.1:p.Arg9Cys
LRG_1076t1:c.76C>T
LRG_1076t2:c.25C>T
LRG_1076:g.8421C>T
LRG_1076p1:p.Arg26Cys
LRG_1076p2:p.Arg9Cys
NC_000011.9:g.118959007C>T
NM_000190.3:c.76C>T

Protein change:

R26C

Links:

dbSNP: rs998842815

NCBI 1000 Genomes Browser:

rs998842815

Molecular consequence:

NM_000190.4:c.76C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001024382.2:c.25C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258208.2:c.76C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258209.2:c.25C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

acyltransferase, partial [Mesorhizobium sp. NWXJ40]
acyltransferase, partial [Mesorhizobium sp. NWXJ40]
gi|1025728037|gb|ANC57706.1|

Protein
Mesorhizobium sp. NWXJ40 acyltransferase (nodA) gene, partial cds
Mesorhizobium sp. NWXJ40 acyltransferase (nodA) gene, partial cds
gi|1025728036|gb|KU216553.1|

Nucleotide
acyltransferase, partial [Mesorhizobium sp. NWXJ31]
acyltransferase, partial [Mesorhizobium sp. NWXJ31]
gi|1025728027|gb|ANC57701.1|

Protein
cytochrome b, partial (mitochondrion) [Crocidura quasielongata]
cytochrome b, partial (mitochondrion) [Crocidura quasielongata]
gi|2325508956|gb|UZC81526.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000939179	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 6, 2023)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 8401516, 9238757, 9281416, 19656452, 11055586, 7757070, 9199558, 10502788, 11831862, 16817012, 18627369, 19292878, 20978940, 24997713, 28492532
SCV002525805	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11055586, 11831862, 16025832, 16817012, 7757070, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000939179

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 6, 2023)

germline

clinical testing

PubMed (15)
[See all records that cite these PMIDs]

SCV002525805

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 1, 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

Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase.

Llewellyn DH, Whatley S, Elder GH.

Hum Mol Genet. 1993 Aug;2(8):1315-6. No abstract available.

PubMed [citation]

PMID:: 8401516

Molecular analysis of porphobilinogen (PBG) deaminase gene mutations in acute intermittent porphyria: first study in patients of Slavic origin.

Rosipal R, Puy H, Lamoril J, Martasek P, Nordmann Y, Deybach JC.

Scand J Clin Lab Invest. 1997 May;57(3):217-24.

PubMed [citation]

PMID:: 9238757

See all PubMed Citations (17)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000939179.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (15)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HMBS protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg26 amino acid residue in HMBS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8401516, 9238757, 9281416, 18627369, 19292878, 19656452, 20978940). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects HMBS function (PMID: 11055586, 19292878). ClinVar contains an entry for this variant (Variation ID: 645443). This missense change has been observed in individuals with acute intermittent porphyria (PMID: 7757070, 9199558, 10502788, 11831862, 16817012, 18627369, 19292878, 20978940, 24997713). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 26 of the HMBS protein (p.Arg26Cys).

#	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, SCV002525805.1

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

Description

PP3, PP4, PM2, PM5, PS4

#	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

ClinVar

Relating variation to medicine