NM_000137.4(FAH):c.879C>A (p.Tyr293Ter) AND Tyrosinemia type I

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jun 26, 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:: RCV003468080.3

Allele description [Variation Report for NM_000137.4(FAH):c.879C>A (p.Tyr293Ter)]

NM_000137.4(FAH):c.879C>A (p.Tyr293Ter)

Gene:

FAH:fumarylacetoacetate hydrolase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q25.1

Genomic location:

Preferred name:

NM_000137.4(FAH):c.879C>A (p.Tyr293Ter)

HGVS:

NC_000015.10:g.80175057C>A
NG_012833.1:g.27059C>A
NM_000137.4:c.879C>AMANE SELECT
NM_001374377.1:c.879C>A
NM_001374380.1:c.879C>A
NP_000128.1:p.Tyr293Ter
NP_001361306.1:p.Tyr293Ter
NP_001361309.1:p.Tyr293Ter
NC_000015.9:g.80467399C>A

Protein change:

Y293*

Molecular consequence:

NM_000137.4:c.879C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001374377.1:c.879C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001374380.1:c.879C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Tyrosinemia type I (TYRSN1)
Synonyms:: Tyrosinemia type 1; Hepatorenal tyrosinemia; FAH deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010161; MedGen: C0268490; Orphanet: 882; OMIM: 276700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004195895	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 26, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004461227	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9101289, 9633815, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004195895

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 26, 2023)

unknown

clinical testing

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

SCV004461227

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2023)

germline

clinical testing

PubMed (3)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview.

St-Louis M, Tanguay RM.

Hum Mutat. 1997;9(4):291-9. Review.

PubMed [citation]

PMID:: 9101289

See all PubMed Citations (4)

Details of each submission

From Baylor Genetics, SCV004195895.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004461227.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Tyr293*) in the FAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAH are known to be pathogenic (PMID: 9101289, 9633815). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with FAH-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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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