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NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
11 (Most recent: Nov 19, 2021)
Last evaluated:
Jan 1, 2021
Accession:
VCV000237048.19
Variation ID:
237048
Description:
single nucleotide variant
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NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala)

Allele ID
242537
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
16q24.3
Genomic location
16: 89746848 (GRCh38) GRCh38 UCSC
16: 89813256 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
O15360:p.Thr1131Ala
LRG_495:g.74810A>G
NC_000016.10:g.89746848T>C
... more HGVS
Protein change
T1131A
Other names
-
Canonical SPDI
NC_000016.10:89746847:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00008
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD) 0.00009
The Genome Aggregation Database (gnomAD), exomes 0.00009
Trans-Omics for Precision Medicine (TOPMed) 0.00009
Links
ClinGen: CA8251197
UniProtKB: O15360#VAR_009653
dbSNP: rs574034197
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Jan 1, 2021 RCV000498721.6
Pathogenic/Likely pathogenic 6 criteria provided, multiple submitters, no conflicts Jan 7, 2020 RCV000665186.6
Pathogenic 1 criteria provided, single submitter Nov 1, 2020 RCV000230300.7
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FANCA - - GRCh38
GRCh37
2162 2653

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 01, 2020)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia
Allele origin: germline
Invitae
Accession: SCV000283560.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces threonine with alanine at codon 1131 of the FANCA protein (p.Thr1131Ala). The threonine residue is highly conserved and there is a … (more)
Likely pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group A
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894100.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(May 30, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000589393.2
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The T1131A variant in the FANCA gene has been reported previously in the homozygous state and with large intragenic deletions in individuals with Fanconi anemia-complementation … (more)
Pathogenic
(Aug 03, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448867.1
Submitted: (Sep 02, 2020)
Evidence details
Pathogenic
(Jan 07, 2020)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group A
Allele origin: maternal
Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001481589.2
Submitted: (Feb 10, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID 9371798, 26556299, 27577878, … (more)
Pathogenic
(Jul 26, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories,Mayo Clinic
Accession: SCV001715181.1
Submitted: (May 26, 2021)
Evidence details
Publications
PubMed (6)
Comment:
PS3, PS4, PM1, PM2,
Likely pathogenic
(Jan 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001501640.3
Submitted: (Jul 04, 2021)
Evidence details
Likely pathogenic
(Jan 17, 2017)
no assertion criteria provided
Method: clinical testing
Fanconi anemia, complementation group A
Allele origin: unknown
Counsyl
Accession: SCV000789260.2
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (8)
Pathogenic
(Feb 28, 2020)
no assertion criteria provided
Method: curation
Fanconi anemia, complementation group A
Allele origin: germline
Leiden Open Variation Database
Accession: SCV001425707.1
Submitted: (Mar 04, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Johan de Winter, Sue Richards.
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Fanconi anemia, group A
Allele origin: germline
Natera, Inc.
Accession: SCV001462879.1
Submitted: (Dec 28, 2020)
Evidence details
Pathogenic
(Jun 12, 2019)
no assertion criteria provided
Method: clinical testing
Fanconi anemia, complementation group A
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002022312.1
Submitted: (Nov 19, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Fatal Myelotoxicity Following Palliative Chemotherapy With Cisplatin and Gemcitabine in a Patient With Stage IV Cholangiocarcinoma Linked to Post Mortem Diagnosis of Fanconi Anemia. Engel NW Frontiers in oncology 2019 PMID: 31192125
A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families. Kimble DC Human mutation 2018 PMID: 29098742
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Maintenance of genome stability by Fanconi anemia proteins. Palovcak A Cell & bioscience 2017 PMID: 28239445
Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. Stray-Pedersen A The Journal of allergy and clinical immunology 2017 PMID: 27577878
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. Schrader KA JAMA oncology 2016 PMID: 26556299
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 Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Xiong HY Science (New York, N.Y.) 2015 PMID: 25525159
Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing. Gille JJ Anemia 2012 PMID: 22778927
Validation of Fanconi anemia complementation Group A assignment using molecular analysis. Moghrabi NN Genetics in medicine : official journal of the American College of Medical Genetics 2009 PMID: 19367192
Diagnosis of Fanconi anemia in patients with bone marrow failure. Pinto FO Haematologica 2009 PMID: 19278965
Genetic subtyping of Fanconi anemia by comprehensive mutation screening. Ameziane N Human mutation 2008 PMID: 17924555
Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study. Levran O Human mutation 2005 PMID: 15643609
Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants. Adachi D Human molecular genetics 2002 PMID: 12444097
Sequence variation in the Fanconi anemia gene FAA. Levran O Proceedings of the National Academy of Sciences of the United States of America 1997 PMID: 9371798
Leucocyte count as an alternative to ESR in general practice? Dinant GJ Scandinavian journal of primary health care 1991 PMID: 1792455

Text-mined citations for rs574034197...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 02, 2021