NM_014324.6(AMACR):c.698T>C (p.Val233Ala) AND Alpha-methylacyl-CoA racemase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 30, 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:: RCV001927817.6

Allele description [Variation Report for NM_014324.6(AMACR):c.698T>C (p.Val233Ala)]

NM_014324.6(AMACR):c.698T>C (p.Val233Ala)

Genes:

C1QTNF3-AMACR:C1QTNF3-AMACR readthrough (NMD candidate) [Gene - HGNC]
AMACR:alpha-methylacyl-CoA racemase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p13.2

Genomic location:

Preferred name:

NM_014324.6(AMACR):c.698T>C (p.Val233Ala)

HGVS:

NC_000005.10:g.33998682A>G
NG_016211.1:g.14434T>C
NM_001167595.2:c.698T>C
NM_014324.6:c.698T>CMANE SELECT
NM_203382.3:c.537T>C
NP_001161067.1:p.Val233Ala
NP_055139.4:p.Val233Ala
NP_976316.1:p.Cys179=
NC_000005.9:g.33998787A>G
NR_037951.1:n.1054T>C

Protein change:

V233A

Links:

dbSNP: rs76184600

NCBI 1000 Genomes Browser:

rs76184600

Molecular consequence:

NM_001167595.2:c.698T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014324.6:c.698T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_037951.1:n.1054T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_203382.3:c.537T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Alpha-methylacyl-CoA racemase deficiency (AMACRD)
Synonyms:: AMACR deficiency
Identifiers:: MONDO: MONDO:0013681; MedGen: C3280428; Orphanet: 79095; OMIM: 614307

Recent activity

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Rattus norvegicus strain BN/NHsdMcwi chromosome 9, GRCr8, whole genome shotgun s...
Rattus norvegicus strain BN/NHsdMcwi chromosome 9, GRCr8, whole genome shotgun sequence
gi|2671914596|gnl|ASM:GCF_036323745 |ref|NC_086027.1||gpp|GPC_000020852.1||gnl|NCBI_GENOMES|157498

Nucleotide
PMC Links for GEO Profiles (Select 119184420) (1)
PMC
Crisp3 cysteine-rich secretory protein 3 [Rattus norvegicus]
Crisp3 cysteine-rich secretory protein 3 [Rattus norvegicus]
Gene ID:64827

Gene
Gene Links for Nucleotide (Select 1937369698) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002173395	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 30, 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

SCV002173395

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 30, 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, SCV002173395.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with AMACR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 233 of the AMACR protein (p.Val233Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine.

#	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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