NM_000187.4(HGD):c.1221G>A (p.Ala407=) AND Alkaptonuria

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Jan 31, 2024
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:: RCV000365826.14

Allele description [Variation Report for NM_000187.4(HGD):c.1221G>A (p.Ala407=)]

NM_000187.4(HGD):c.1221G>A (p.Ala407=)

Gene:

HGD:homogentisate 1,2-dioxygenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q13.33

Genomic location:

Preferred name:

NM_000187.4(HGD):c.1221G>A (p.Ala407=)

HGVS:

NC_000003.12:g.120628497C>T
NG_011957.1:g.58985G>A
NM_000187.4:c.1221G>AMANE SELECT
NP_000178.2:p.Ala407=
NC_000003.11:g.120347344C>T
NM_000187.3:c.1221G>A

Links:

dbSNP: rs146206905

NCBI 1000 Genomes Browser:

rs146206905

Molecular consequence:

NM_000187.4:c.1221G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Alkaptonuria (AKU)
Synonyms:: HOMOGENTISIC ACID OXIDASE DEFICIENCY; Alcaptonuria; Ochronosis, hereditary; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008753; MedGen: C0002066; Orphanet: 56; OMIM: 203500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000439979	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001115883	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004101017	Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	no assertion criteria provided	Pathogenic	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000439979

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV001115883

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 31, 2024)

germline

clinical testing

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

SCV004101017

Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences

no assertion criteria provided

Pathogenic

germline

research

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
not provided	germline	yes	1	1	not provided	not provided	yes	research

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

Ochronotic rheumatism in Algeria: clinical, radiological, biological and molecular studies--a case study of 14 patients in 11 families.

Ladjouze-Rezig A, Rodriguez de Cordoba S, Aquaron R.

Joint Bone Spine. 2006 May;73(3):284-92. Epub 2005 Jul 7.

PubMed [citation]

PMID:: 16085442

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000439979.3

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001115883.6

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

#	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 Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences, SCV004101017.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	yes	research	PubMed (1)

Description

The variant was originally described in AKU patient in PMID:16085442, as a silent variant affecting splicing. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00103).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Jan 13, 2025

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