NM_000137.4(FAH):c.1062+5G>A AND FAH-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 22, 2023
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:: RCV003407317.5

Allele description [Variation Report for NM_000137.4(FAH):c.1062+5G>A]

NM_000137.4(FAH):c.1062+5G>A

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.1062+5G>A

Other names:

IVS12+5 G>A

HGVS:

NC_000015.10:g.80180230G>A
NG_012833.1:g.32232G>A
NM_000137.2:c.[1062+5G>A]
NM_000137.4:c.1062+5G>AMANE SELECT
NM_001374377.1:c.1062+5G>A
NM_001374380.1:c.1062+5G>A
NC_000015.9:g.80472572G>A
NM_000137.1:c.1062+5G>A
NM_000137.2:c.1062+5G>A
NM_000137.2:c.[1062+5G>A]
NM_000137.3:c.1062+5G>A
NM_000137.4:c.1062+5G>A
c.1062+5G>A

Nucleotide change:

IVS12DS, G-A, +5

Links:

OMIM: 613871.0003; dbSNP: rs80338901

NCBI 1000 Genomes Browser:

rs80338901

Molecular consequence:

NM_000137.4:c.1062+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374377.1:c.1062+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374380.1:c.1062+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: FAH-related disorder
Synonyms:: FAH-related condition
Identifiers:

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gi|2787449678|tpg|BK068166.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004113967	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 22, 2023)	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

SCV004113967

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 22, 2023)

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

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004113967.1

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

Description

The FAH c.1062+5G>A variant is predicted to interfere with splicing. This variant has been well documented to be causative for tyrosinemia type I (also referred to as IVS12+5G>A; Grompe and al-Dhalimy. 1993. PubMed ID: 8318997; Pérez-Carro et al. 2014. PubMed ID: 23895425) and is particularly prevalent in the French Canadian and Northern European populations (Poudrier et al. 1996. PubMed ID: 8821854; Sheth et al. 2012. PubMed ID: 23193487). Using minigene analysis, the c.1062+5G>A variant was shown to result in exon skipping (Pérez-Carro et al. 2014. PubMed ID: 23895425). This variant is interpreted as pathogenic or likely pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/11870/). This variant is reported in 0.066% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-80472572-G-A). This variant is interpreted as pathogenic.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine