NM_000375.3(UROS):c.7G>T (p.Val3Phe) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 14, 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:: RCV001377883.6

Allele description [Variation Report for NM_000375.3(UROS):c.7G>T (p.Val3Phe)]

NM_000375.3(UROS):c.7G>T (p.Val3Phe)

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.7G>T (p.Val3Phe)

HGVS:

NC_000010.11:g.125816493C>A
NG_011557.2:g.11776G>T
NM_000375.3:c.7G>TMANE SELECT
NM_001324036.2:c.7G>T
NM_001324037.2:c.7G>T
NM_001324038.2:c.7G>T
NM_001324039.2:c.7G>T
NP_000366.1:p.Val3Phe
NP_001310965.1:p.Val3Phe
NP_001310966.1:p.Val3Phe
NP_001310967.1:p.Val3Phe
NP_001310968.1:p.Val3Phe
LRG_1081t1:c.7G>T
LRG_1081:g.11776G>T
LRG_1081p1:p.Val3Phe
NC_000010.10:g.127505062C>A
NR_136675.2:n.263G>T
NR_136676.2:n.263G>T
NR_136677.2:n.263G>T

Protein change:

V3F

Links:

dbSNP: rs773301339

NCBI 1000 Genomes Browser:

rs773301339

Molecular consequence:

NM_000375.3:c.7G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001324036.2:c.7G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001324037.2:c.7G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001324038.2:c.7G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001324039.2:c.7G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_136675.2:n.263G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136676.2:n.263G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136677.2:n.263G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001575330	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9188670, 23626549, 19099412, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001575330

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (4)
[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

Novel point mutation in the uroporphyrinogen III synthase gene causes congenital erythropoietic porphyria of a Japanese family.

Takamura N, Hombrados I, Tanigawa K, Namba H, Nagayama Y, de Verneuil H, Yamashita S.

Am J Med Genet. 1997 Jun 13;70(3):299-302.

PubMed [citation]

PMID:: 9188670

Congenital Erythropoietic Porphyria: Mutation of the Uroporphyrinogen III Cosynthase Gene in a Vietnamese Patient.

Thien Kim DH, Kawazoe A, Bang PD, Thanh NT, Taketani S.

Case Rep Dermatol. 2013 Mar 27;5(1):105-10. doi: 10.1159/000350679. Print 2013 Jan.

PubMed [citation]

PMID:: 23626549
PMCID:: PMC3635963

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001575330.4

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

Description

This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 3 of the UROS protein (p.Val3Phe). This variant is present in population databases (rs773301339, gnomAD 0.006%). This missense change has been observed in individual(s) with congenital erythropoietic porphyria (PMID: 9188670, 23626549; Invitae). ClinVar contains an entry for this variant (Variation ID: 1066786). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects UROS function (PMID: 19099412). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Feb 20, 2024

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