NM_014336.5(AIPL1):c.157C>T (p.Arg53Trp) AND Leber congenital amaurosis 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 11, 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:: RCV001222809.7

Allele description [Variation Report for NM_014336.5(AIPL1):c.157C>T (p.Arg53Trp)]

NM_014336.5(AIPL1):c.157C>T (p.Arg53Trp)

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.157C>T (p.Arg53Trp)

HGVS:

NC_000017.11:g.6434038G>A
NG_008474.1:g.6162C>T
NM_001033054.3:c.157C>T
NM_001033055.3:c.96+971C>T
NM_001285399.3:c.121C>T
NM_001285400.3:c.97-6C>T
NM_001285401.3:c.157C>T
NM_001285402.2:c.40C>T
NM_001285403.4:c.157C>T
NM_014336.5:c.157C>TMANE SELECT
NP_001028226.1:p.Arg53Trp
NP_001272328.1:p.Arg41Trp
NP_001272330.1:p.Arg53Trp
NP_001272331.1:p.Arg14Trp
NP_001272332.1:p.Arg53Trp
NP_055151.3:p.Arg53Trp
NC_000017.10:g.6337358G>A
NM_014336.3:c.157C>T
NM_014336.4:c.157C>T

Protein change:

R14W

Links:

dbSNP: rs62637008

NCBI 1000 Genomes Browser:

rs62637008

Molecular consequence:

NM_001033055.3:c.96+971C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001285400.3:c.97-6C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001033054.3:c.157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285399.3:c.121C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285401.3:c.157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285402.2:c.40C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285403.4:c.157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014336.5:c.157C>T - 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
SCV001394926	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33067476, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001394926

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 11, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Clinical and functional analyses of AIPL1 variants reveal mechanisms of pathogenicity linked to different forms of retinal degeneration.

Sacristan-Reviriego A, Le HM, Georgiou M, Meunier I, Bocquet B, Roux AF, Prodromou C, Bainbridge J, Michaelides M, van der Spuy J.

Sci Rep. 2020 Oct 16;10(1):17520. doi: 10.1038/s41598-020-74516-9.

PubMed [citation]

PMID:: 33067476
PMCID:: PMC7567831

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, SCV001394926.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 53 of the AIPL1 protein (p.Arg53Trp). This variant is present in population databases (rs62637008, gnomAD 0.007%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 33067476). ClinVar contains an entry for this variant (Variation ID: 99790). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Studies have shown that this missense change alters AIPL1 gene expression (PMID: 33067476). 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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