NM_080669.6(SLC46A1):c.1082-1G>A AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 25, 2022
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:: RCV002512627.2

Allele description [Variation Report for NM_080669.6(SLC46A1):c.1082-1G>A]

NM_080669.6(SLC46A1):c.1082-1G>A

Genes:

SLC46A1:solute carrier family 46 member 1 [Gene - OMIM - HGNC]
SARM1:sterile alpha and TIR motif containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_080669.6(SLC46A1):c.1082-1G>A

HGVS:

NC_000017.11:g.28402322C>T
NG_013306.1:g.8889G>A
NG_136053.1:g.294C>T
NM_001242366.3:c.1082-1556G>A
NM_015077.4:c.*6036C>TMANE SELECT
NM_080669.6:c.1082-1G>AMANE SELECT
LRG_183t1:c.1082-1G>A
LRG_183:g.8889G>A
NC_000017.10:g.26729340C>T
NM_080669.3:c.1082-1G>A
NM_080669.4:c.1082-1G>A
NM_080669.5:c.1082-1G>A

Nucleotide change:

IVS2AS, G-A, -1

Links:

OMIM: 611672.0001; dbSNP: rs80338775

NCBI 1000 Genomes Browser:

rs80338775

Molecular consequence:

NM_015077.4:c.*6036C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001242366.3:c.1082-1556G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_080669.6:c.1082-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003742111	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 25, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11807405, 17129779, 19740703, 21489556 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003742111

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 25, 2022)

germline

clinical testing

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

Citation Link

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

Hereditary folate malabsorption: family report and review of the literature.

Geller J, Kronn D, Jayabose S, Sandoval C.

Medicine (Baltimore). 2002 Jan;81(1):51-68. Review. No abstract available.

PubMed [citation]

PMID:: 11807405

Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption.

Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID.

Cell. 2006 Dec 1;127(5):917-28.

PubMed [citation]

PMID:: 17129779

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV003742111.2

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

Description

The c.1082-1G>A intronic alteration consists of a G to A substitution one nucleotide before exon 3 (coding exon 3) of the SLC46A1 gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. Based on data from gnomAD, the A allele has an overall frequency of 0.001% (2/275882) total alleles studied. This variant has been identified in the homozygous state in multiple individuals diagnosed with hereditary folate malabsorption (Mahadeo, 2011; Borzutzky, 2009; Geller, 2002). This nucleotide position is highly conserved in available vertebrate species. RNA studies demonstrate this alteration leads to abnormal splicing in the set of samples tested (Qiu, 2006). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Based on the available evidence, this alteration is classified 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 13, 2024

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