NM_000190.4(HMBS):c.163G>T (p.Ala55Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 2023
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:: RCV003234886.1

Allele description [Variation Report for NM_000190.4(HMBS):c.163G>T (p.Ala55Ser)]

NM_000190.4(HMBS):c.163G>T (p.Ala55Ser)

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.163G>T (p.Ala55Ser)

HGVS:

NC_000011.10:g.119089084G>T
NG_008093.1:g.9208G>T
NM_000190.4:c.163G>TMANE SELECT
NM_001024382.2:c.112G>T
NM_001258208.2:c.163G>T
NM_001258209.2:c.112G>T
NP_000181.2:p.Ala55Ser
NP_001019553.1:p.Ala38Ser
NP_001245137.1:p.Ala55Ser
NP_001245138.1:p.Ala38Ser
LRG_1076t1:c.163G>T
LRG_1076t2:c.112G>T
LRG_1076:g.9208G>T
LRG_1076p1:p.Ala55Ser
LRG_1076p2:p.Ala38Ser
NC_000011.9:g.118959794G>T
NM_000190.3:c.163G>T
P08397:p.Ala55Ser

Protein change:

A38S; ALA55SER

Links:

UniProtKB: P08397#VAR_003642; OMIM: 609806.0018; dbSNP: rs118204106

NCBI 1000 Genomes Browser:

rs118204106

Molecular consequence:

NM_000190.4:c.163G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001024382.2:c.112G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258208.2:c.163G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258209.2:c.112G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

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
SCV003934345	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 8270254, 9199558 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003934345

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 22, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis.

Gu XF, de Rooij F, Voortman G, Te Velde K, Deybach JC, Nordmann Y, Grandchamp B.

Hum Genet. 1994 Jan;93(1):47-52.

PubMed [citation]

PMID:: 8270254

Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.

Puy H, Deybach JC, Lamoril J, Robreau AM, Da Silva V, Gouya L, Grandchamp B, Nordmann Y.

Am J Hum Genet. 1997 Jun;60(6):1373-83.

PubMed [citation]

PMID:: 9199558
PMCID:: PMC1716106

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003934345.1

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

Description

Variant summary: HMBS c.163G>T (p.Ala55Ser) results in a conservative amino acid change located in the Porphobilinogen deaminase, N-terminal domain (IPR022417) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251494 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.163G>T has been reported in the literature in individuals affected with Acute Intermittent Porphyria (e.g. Gu_1994, Puy_1997). These reports do not provide unequivocal conclusions about association of the variant with Acute Intermittent Porphyria. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 8270254, 9199558). One ClinVar submitter has assessed the variant since 2014: the variant was classified as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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

ClinVar

Relating variation to medicine