NM_000375.3(UROS):c.337G>C (p.Asp113His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 19, 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:: RCV002019810.5

Allele description [Variation Report for NM_000375.3(UROS):c.337G>C (p.Asp113His)]

NM_000375.3(UROS):c.337G>C (p.Asp113His)

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.337G>C (p.Asp113His)

Other names:

p.Asp113His

HGVS:

NC_000010.11:g.125807470C>G
NG_011557.2:g.20799G>C
NM_000375.3:c.337G>CMANE SELECT
NM_001324036.2:c.337G>C
NM_001324037.2:c.337G>C
NM_001324038.2:c.337G>C
NM_001324039.2:c.337G>C
NP_000366.1:p.Asp113His
NP_001310965.1:p.Asp113His
NP_001310966.1:p.Asp113His
NP_001310967.1:p.Asp113His
NP_001310968.1:p.Asp113His
LRG_1081t1:c.337G>C
LRG_1081:g.20799G>C
LRG_1081p1:p.Asp113His
NC_000010.10:g.127496039C>G
NR_136675.2:n.412G>C
NR_136676.2:n.593G>C
NR_136677.2:n.593G>C
NR_136678.2:n.323G>C

Protein change:

D113H

Links:

dbSNP: rs754414355

NCBI 1000 Genomes Browser:

rs754414355

Molecular consequence:

NM_000375.3:c.337G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324036.2:c.337G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324037.2:c.337G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324038.2:c.337G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324039.2:c.337G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136675.2:n.412G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136676.2:n.593G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136677.2:n.593G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_136678.2:n.323G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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
SCV002285640	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 7, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225340	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 19, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002285640

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 7, 2022)

germline

clinical testing

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

SCV004225340

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 19, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV002285640.2

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 113 of the UROS protein (p.Asp113His). This variant is present in population databases (rs754414355, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with UROS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1497350). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004225340.1

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

Description

BP4

#	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		2	not provided	not provided	not provided

Last Updated: Jan 6, 2024

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