NM_003977.4(AIP):c.490C>T (p.Gln164Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 26, 2019
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:: RCV001023250.3

Allele description [Variation Report for NM_003977.4(AIP):c.490C>T (p.Gln164Ter)]

NM_003977.4(AIP):c.490C>T (p.Gln164Ter)

Gene:

AIP:aryl hydrocarbon receptor interacting protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_003977.4(AIP):c.490C>T (p.Gln164Ter)

HGVS:

NC_000011.10:g.67490059C>T
NG_008969.1:g.12026C>T
NM_001302959.2:c.313C>T
NM_001302960.2:c.490C>T
NM_003977.4:c.490C>TMANE SELECT
NP_001289888.1:p.Gln105Ter
NP_001289889.1:p.Gln164Ter
NP_003968.3:p.Gln164Ter
LRG_460t1:c.490C>T
LRG_460:g.12026C>T
NC_000011.9:g.67257530C>T
NM_003977.2:c.490C>T

Protein change:

Q105*

Links:

dbSNP: rs104895073

NCBI 1000 Genomes Browser:

rs104895073

Molecular consequence:

NM_001302959.2:c.313C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001302960.2:c.490C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003977.4:c.490C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001185099	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 26, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20506337, 21348957, 25093619, 26186299 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185099

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 26, 2019)

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

Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.

Igreja S, Chahal HS, King P, Bolger GB, Srirangalingam U, Guasti L, Chapple JP, Trivellin G, Gueorguiev M, Guegan K, Stals K, Khoo B, Kumar AV, Ellard S, Grossman AB, Korbonits M; International FIPA Consortium..

Hum Mutat. 2010 Aug;31(8):950-60. doi: 10.1002/humu.21292.

PubMed [citation]

PMID:: 20506337
PMCID:: PMC3065644

Familial isolated pituitary adenomas: from genetics to therapy.

Guaraldi F, Salvatori R.

Clin Transl Sci. 2011 Feb;4(1):55-62. doi: 10.1111/j.1752-8062.2010.00254.x. Review.

PubMed [citation]

PMID:: 21348957
PMCID:: PMC5439841

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV001185099.4

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

Description

The p.Q164* variant (also known as c.490C>T), located in coding exon 4 of the AIP gene, results from a C to T substitution at nucleotide position 490. This changes the amino acid from a glutamine to a stop codon within coding exon 4. One study found that this mutation drastically reduced the protein-protein binding activity of the AIP protein and identified this alteration in 1/38 familial isolated pituitary adenoma (FIPA) families (Igreja S et al. Hum. Mutat., 2010 Aug;31:950-60). This mutation has also been reported in additional individuals with FIPA (Hernández-Ramírez LC et al. J. Clin. Endocrinol. Metab., 2015 Sep;100:E1242-54) and in a German patient with acromegaly and pituitary macroadenoma diagnosed at age 18 (Schöfl C et al. J. Clin. Endocrinol. Metab., 2014 Dec;99:E2789-93). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: May 1, 2024

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