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NM_000137.4(FAH):c.615del (p.Phe205fs) AND Tyrosinemia type I

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Mar 20, 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:
RCV000409747.5

Allele description [Variation Report for NM_000137.4(FAH):c.615del (p.Phe205fs)]

NM_000137.4(FAH):c.615del (p.Phe205fs)

Gene:
FAH:fumarylacetoacetate hydrolase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q25.1
Genomic location:
Preferred name:
NM_000137.4(FAH):c.615del (p.Phe205fs)
HGVS:
  • NC_000015.10:g.80172157del
  • NG_012833.1:g.24159del
  • NM_000137.4:c.615delMANE SELECT
  • NM_001374377.1:c.615del
  • NM_001374380.1:c.615del
  • NP_000128.1:p.Phe205fs
  • NP_000128.1:p.Phe205fs
  • NP_001361306.1:p.Phe205fs
  • NP_001361309.1:p.Phe205fs
  • NC_000015.9:g.80464493del
  • NC_000015.9:g.80464499del
  • NM_000137.2:c.615delT
  • NM_000137.3:c.615del
Protein change:
F205fs
Links:
dbSNP: rs1057517084
NCBI 1000 Genomes Browser:
rs1057517084
Molecular consequence:
  • NM_000137.4:c.615del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001374377.1:c.615del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001374380.1:c.615del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000486722Counsyl
criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))
Likely pathogenic
(Jul 26, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001810422Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jul 22, 2021)
germlineclinical testing

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

SCV004297664Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Mar 20, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Hereditary tyrosinaemia type I in Norway: incidence and three novel small deletions in the fumarylacetoacetase gene.

Bliksrud YT, Brodtkorb E, Backe PH, Woldseth B, Rootwelt H.

Scand J Clin Lab Invest. 2012 Sep;72(5):369-73. doi: 10.3109/00365513.2012.676210. Epub 2012 May 4.

PubMed [citation]
PMID:
22554029
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000486722.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV001810422.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV004297664.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 371201). This premature translational stop signal has been observed in individual(s) with tyrosinemia type 1 (PMID: 22554029). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe205Leufs*2) 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024