NM_000375.3(UROS):c.-26-193C>A AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 27, 2021
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:: RCV001851634.6

Allele description [Variation Report for NM_000375.3(UROS):c.-26-193C>A]

NM_000375.3(UROS):c.-26-193C>A

Gene:

UROS:uroporphyrinogen III synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.2

Genomic location:

Preferred name:

NM_000375.3(UROS):c.-26-193C>A

HGVS:

NC_000010.11:g.125816718G>T
NG_011557.2:g.11551C>A
NM_000375.3:c.-26-193C>AMANE SELECT
NM_001324036.2:c.-26-193C>A
NM_001324037.2:c.-26-193C>A
NM_001324038.2:c.-26-193C>A
NM_001324039.2:c.-26-193C>A
LRG_1081t1:c.-26-193C>A
LRG_1081:g.11551C>A
NC_000010.10:g.127505287G>T
AH010036.2:c.-3271T>C(-86C>A)

Nucleotide change:

-86C-A

Links:

OMIM: 606938.0015; dbSNP: rs397515350

NCBI 1000 Genomes Browser:

rs397515350

Molecular consequence:

NM_000375.3:c.-26-193C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001324036.2:c.-26-193C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001324037.2:c.-26-193C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001324038.2:c.-26-193C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001324039.2:c.-26-193C>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002233173	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 27, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11254675, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002233173

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 27, 2021)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Uroporphyrinogen III synthase erythroid promoter mutations in adjacent GATA1 and CP2 elements cause congenital erythropoietic porphyria.

Solis C, Aizencang GI, Astrin KH, Bishop DF, Desnick RJ.

J Clin Invest. 2001 Mar;107(6):753-62.

PubMed [citation]

PMID:: 11254675
PMCID:: PMC208941

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002233173.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects UROS protein function (PMID: 11254675). This variant has been observed in individual(s) with congenital erythropoietic porphyria (PMID: 11254675). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as -86C>A. ClinVar contains an entry for this variant (Variation ID: 3764). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change falls in intron 1 of the UROS gene. It does not directly change the encoded amino acid sequence of the UROS 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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