NM_000137.3(FAH):c.1063-2A>G AND Tyrosinemia type I

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 4, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000674452.2

Allele description [Variation Report for NM_000137.3(FAH):c.1063-2A>G]

NM_000137.3(FAH):c.1063-2A>G

Gene:
FAH:fumarylacetoacetate hydrolase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q25.1
Genomic location:
Preferred name:
NM_000137.3(FAH):c.1063-2A>G
HGVS:
  • NC_000015.10:g.80181040A>G
  • NG_012833.1:g.33042A>G
  • NM_000137.3:c.1063-2A>G
  • NC_000015.9:g.80473382A>G
  • NM_000137.2:c.1063-2A>G
Links:
dbSNP: rs1555442385
NCBI 1000 Genomes Browser:
rs1555442385
Molecular consequence:
  • NM_000137.3:c.1063-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000799790Counsylcriteria provided, single submitter
Likely pathogenic
(May 10, 2018)
unknownclinical testing

Citation Link,

SCV001592922Invitaecriteria provided, single submitter
Pathogenic
(Mar 4, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

Mak CM, Lam CW, Chim S, Siu TS, Ng KF, Tam S.

Clin Biochem. 2013 Jan;46(1-2):155-9. doi: 10.1016/j.clinbiochem.2012.09.010. Epub 2012 Sep 18.

PubMed [citation]
PMID:
23000314

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000799790.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001592922.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects an acceptor splice site in intron 12 of the FAH gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with tyrosinemia type I (PMID: 23000314). ClinVar contains an entry for this variant (Variation ID: 558219). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FAH are known to be pathogenic (PMID: 9101289, 9633815). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

Support Center