NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala) AND Fanconi anemia complementation group A

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: May 26, 2022
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:: RCV000665186.16

Allele description [Variation Report for NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala)]

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

Genes:

FANCA:FA complementation group A [Gene - OMIM - HGNC]
LOC132090450:Neanderthal introgressed variant-containing enhancer experimental_46718 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

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

HGVS:

NC_000016.10:g.89746848T>C
NG_011706.1:g.74810A>G
NM_000135.4:c.3391A>GMANE SELECT
NM_001286167.3:c.3391A>G
NP_000126.2:p.Thr1131Ala
NP_001273096.1:p.Thr1131Ala
LRG_495t1:c.3391A>G
LRG_495:g.74810A>G
NC_000016.9:g.89813256T>C
NM_000135.2:c.3391A>G
NM_000135.3:c.3391A>G
O15360:p.Thr1131Ala

Protein change:

T1131A

Links:

UniProtKB: O15360#VAR_009653; dbSNP: rs574034197

NCBI 1000 Genomes Browser:

rs574034197

Molecular consequence:

NM_000135.4:c.3391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286167.3:c.3391A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fanconi anemia complementation group A
Synonyms:: Fanconi anemia, group A
Identifiers:: MONDO: MONDO:0009215; MedGen: C3469521; Orphanet: 84; OMIM: 227650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000894100	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 26, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001425707	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (Feb 28, 2020)	germline	curation	PubMed (4) [See all records that cite these PMIDs] 12444097, 15643609, 17924555, 22778927
SCV001462879	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV001481589	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 7, 2020)	maternal	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9371798, 26556299, 27577878, 25525159, 25741868
SCV002022312	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 12, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002060324	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Pathogenic (Oct 1, 2021)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15643609, 19367192, 19278965, 22778927, 12444097 Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
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
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic subtyping of Fanconi anemia by comprehensive mutation screening.

Ameziane N, Errami A, Léveillé F, Fontaine C, de Vries Y, van Spaendonk RM, de Winter JP, Pals G, Joenje H.

Hum Mutat. 2008 Jan;29(1):159-66.

PubMed [citation]

PMID:: 17924555

Sequence variation in the Fanconi anemia gene FAA.

Levran O, Erlich T, Magdalena N, Gregory JJ, Batish SD, Verlander PC, Auerbach AD.

Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13051-6.

PubMed [citation]

PMID:: 9371798
PMCID:: PMC24261

See all PubMed Citations (11)

PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000894100.2

#	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 Leiden Open Variation Database, SCV001425707.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (4)

Description

Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Johan de Winter, Sue Richards.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV001462879.1

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

#	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

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV001481589.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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, 25525159, ClinVar ID: 237048]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002022312.3

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

From Myriad Genetics, Inc., SCV002060324.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

NM_000135.2(FANCA):c.3391A>G(T1131A) is a missense variant classified as pathogenic in the context of Fanconi anemia complementation group A. T1131A has been observed in cases with relevant disease (PMID: 22778927, 19367192, 15643609, 19278965, 19367192). Functional assessments of this variant are available in the literature (PMID: 12444097). T1131A has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, NM_000135.2(FANCA):c.3391A>G(T1131A) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

#	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

Last Updated: Apr 15, 2024

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