NM_014336.5(AIPL1):c.1058A>G (p.Glu353Gly) AND Leber congenital amaurosis 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 23, 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:: RCV002046905.3

Allele description [Variation Report for NM_014336.5(AIPL1):c.1058A>G (p.Glu353Gly)]

NM_014336.5(AIPL1):c.1058A>G (p.Glu353Gly)

Gene:

AIPL1:aryl hydrocarbon receptor interacting protein like 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_014336.5(AIPL1):c.1058A>G (p.Glu353Gly)

HGVS:

NC_000017.11:g.6425557T>C
NG_008474.1:g.14643A>G
NM_001033054.3:c.869A>G
NM_001033055.3:c.878A>G
NM_001285399.3:c.1022A>G
NM_001285400.3:c.992A>G
NM_001285401.3:c.986A>G
NM_001285402.2:c.941A>G
NM_001285403.4:c.*1029A>G
NM_014336.3:c.1058A>G
NM_014336.5:c.1058A>GMANE SELECT
NP_001028226.1:p.Glu290Gly
NP_001028227.1:p.Glu293Gly
NP_001272328.1:p.Glu341Gly
NP_001272329.1:p.Glu331Gly
NP_001272330.1:p.Glu329Gly
NP_001272331.1:p.Glu314Gly
NP_055151.3:p.Glu353Gly
NC_000017.10:g.6328877T>C

Protein change:

E290G

Links:

dbSNP: rs1452332999

NCBI 1000 Genomes Browser:

rs1452332999

Molecular consequence:

NM_001285403.4:c.*1029A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001033054.3:c.869A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001033055.3:c.878A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001285399.3:c.1022A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001285400.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001285401.3:c.986A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001285402.2:c.941A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014336.5:c.1058A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Leber congenital amaurosis 4 (LCA4)
Synonyms:: Amaurosis congenita of Leber, type 4
Identifiers:: MONDO: MONDO:0011458; MedGen: C1858386; OMIM: 604393

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002113434	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002113434

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 23, 2022)

germline

clinical testing

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

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

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, SCV002113434.2

#	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 glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 353 of the AIPL1 protein (p.Glu353Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AIPL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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

Last Updated: Sep 29, 2024

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