NM_003977.4(AIP):c.724C>G (p.Leu242Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 28, 2023
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:: RCV001316992.6

Allele description [Variation Report for NM_003977.4(AIP):c.724C>G (p.Leu242Val)]

NM_003977.4(AIP):c.724C>G (p.Leu242Val)

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.724C>G (p.Leu242Val)

HGVS:

NC_000011.10:g.67490394C>G
NG_008969.1:g.12361C>G
NM_001302959.2:c.547C>G
NM_001302960.2:c.724C>G
NM_003977.4:c.724C>GMANE SELECT
NP_001289888.1:p.Leu183Val
NP_001289889.1:p.Leu242Val
NP_003968.3:p.Leu242Val
LRG_460t1:c.724C>G
LRG_460:g.12361C>G
NC_000011.9:g.67257865C>G
NM_003977.2:c.724C>G

Protein change:

L183V

Links:

dbSNP: rs772782309

NCBI 1000 Genomes Browser:

rs772782309

Molecular consequence:

NM_001302959.2:c.547C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001302960.2:c.724C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003977.4:c.724C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Homo sapiens solute carrier family 16 member 12 (SLC16A12), transcrip...
PREDICTED: Homo sapiens solute carrier family 16 member 12 (SLC16A12), transcript variant X5, mRNA
gi|2217277220|ref|XM_047425222.1|

Nucleotide
monocarboxylate transporter 12 isoform X1 [Homo sapiens]
monocarboxylate transporter 12 isoform X1 [Homo sapiens]
gi|1034568220|ref|XP_016871728.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001507634	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004170311	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 9, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001507634

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 28, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004170311

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 9, 2023)

germline

clinical testing

Citation Link

Help

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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001507634.4

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 242 of the AIP protein (p.Leu242Val). This variant is present in population databases (rs772782309, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with AIP-related conditions. ClinVar contains an entry for this variant (Variation ID: 826929). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AIP protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 GeneDx, SCV004170311.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	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

Last Updated: Sep 29, 2024

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