U.S. flag

An official website of the United States government

NM_000190.4(HMBS):c.962G>A (p.Arg321His) AND not provided

Germline classification:
Conflicting classifications of pathogenicity (5 submissions)
Last evaluated:
Feb 2, 2025
Review status:
criteria provided, conflicting classifications
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:
RCV000730694.24

Allele description [Variation Report for NM_000190.4(HMBS):c.962G>A (p.Arg321His)]

NM_000190.4(HMBS):c.962G>A (p.Arg321His)

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.962G>A (p.Arg321His)
HGVS:
  • NC_000011.10:g.119093159G>A
  • NG_008093.1:g.13283G>A
  • NM_000190.4:c.962G>AMANE SELECT
  • NM_001024382.2:c.911G>A
  • NM_001258208.2:c.842G>A
  • NM_001258209.2:c.791G>A
  • NP_000181.2:p.Arg321His
  • NP_001019553.1:p.Arg304His
  • NP_001245137.1:p.Arg281His
  • NP_001245138.1:p.Arg264His
  • LRG_1076t1:c.962G>A
  • LRG_1076t2:c.911G>A
  • LRG_1076:g.13283G>A
  • LRG_1076p1:p.Arg321His
  • LRG_1076p2:p.Arg304His
  • NC_000011.9:g.118963869G>A
  • NM_000190.3:c.962G>A
Protein change:
R264H
Links:
dbSNP: rs150428209
NCBI 1000 Genomes Browser:
rs150428209
Molecular consequence:
  • NM_000190.4:c.962G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024382.2:c.911G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258208.2:c.842G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258209.2:c.791G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000858452Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Uncertain significance
(Nov 30, 2017)
germlineclinical testing

Citation Link,

SCV001051958Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely benign
(Feb 2, 2025)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001764085GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Likely benign
(Oct 27, 2020)
germlineclinical testing

Citation Link,

SCV001807788Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus
no assertion criteria provided
Likely benigngermlineclinical testing

SCV001955990Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Likely benigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Eurofins Ntd Llc (ga), SCV000858452.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001051958.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001764085.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Reported previously in a 36-year-old Swiss male with acute intermittent porphyria and low-normal hydroxymethylbilane synthase (aka PBG deaminase) activity (Schuurmans et al., 2001); Reported in cis with an HMBS splicing variant in a 63-year-old German male with abdominal pain, paralytic attacks of the right extremities, depression, and reduced hydroxymethylbilane synthase activity that was 40% of normal levels (von Brasch et al., 2004); Published functional studies demonstrate no damaging effect (Lenglet et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30556376, 29360981, 22190498, 27769855, 26075277, 17298216, 27539938, 11591889, 25637381, 15003823)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807788.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001955990.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 13, 2025