NM_000203.5(IDUA):c.812C>T (p.Ser271Phe) AND Mucopolysaccharidosis type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 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:: RCV000793555.6

Allele description [Variation Report for NM_000203.5(IDUA):c.812C>T (p.Ser271Phe)]

NM_000203.5(IDUA):c.812C>T (p.Ser271Phe)

Gene:

IDUA:alpha-L-iduronidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000203.5(IDUA):c.812C>T (p.Ser271Phe)

HGVS:

NC_000004.12:g.1002001C>T
NG_008103.1:g.20005C>T
NM_000203.5:c.812C>TMANE SELECT
NM_001363576.1:c.416C>T
NP_000194.2:p.Ser271Phe
NP_001350505.1:p.Ser139Phe
LRG_1277t1:c.812C>T
LRG_1277:g.20005C>T
LRG_1277p1:p.Ser271Phe
NC_000004.11:g.995789C>T
NM_000203.4:c.812C>T
NR_110313.1:n.900C>T

Protein change:

S139F

Links:

dbSNP: rs766950553

NCBI 1000 Genomes Browser:

rs766950553

Molecular consequence:

NM_000203.5:c.812C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363576.1:c.416C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110313.1:n.900C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis type 1
Synonyms:: Mucopolysaccharidosis type I; MPS 1; Attenuated MPS I (subtype); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0001586; MedGen: C0023786

Recent activity

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leucine-rich repeat transmembrane neuronal protein 4 isoform b precursor [Homo s...
leucine-rich repeat transmembrane neuronal protein 4 isoform b precursor [Homo sapiens]
gi|156139147|ref|NP_079269.4|

Protein
JGI_CAAP6767.fwd NIH_XGC_tropInt1 Xenopus tropicalis cDNA clone IMAGE:7713206 5'...
JGI_CAAP6767.fwd NIH_XGC_tropInt1 Xenopus tropicalis cDNA clone IMAGE:7713206 5', mRNA sequence
gi|58784668|gnl|dbEST|27678060|gb|C 46.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000932913	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	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

SCV000932913

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

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	not provided	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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000932913.3

#	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 serine with phenylalanine at codon 271 of the IDUA protein (p.Ser271Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs766950553, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with IDUA-related conditions. 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 phenylalanine 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

Last Updated: Sep 29, 2024

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