NM_004744.5(LRAT):c.346T>C (p.Phe116Leu) AND Leber congenital amaurosis 14

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 22, 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:: RCV002250709.1

Allele description [Variation Report for NM_004744.5(LRAT):c.346T>C (p.Phe116Leu)]

NM_004744.5(LRAT):c.346T>C (p.Phe116Leu)

Gene:

LRAT:lecithin retinol acyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q32.1

Genomic location:

Preferred name:

NM_004744.5(LRAT):c.346T>C (p.Phe116Leu)

HGVS:

NC_000004.12:g.154744672T>C
NG_009110.1:g.5662T>C
NM_001301645.2:c.346T>C
NM_004744.5:c.346T>CMANE SELECT
NP_001288574.1:p.Phe116Leu
NP_004735.2:p.Phe116Leu
NC_000004.11:g.155665824T>C

Protein change:

F116L

Links:

dbSNP: rs1578860322

NCBI 1000 Genomes Browser:

rs1578860322

Molecular consequence:

NM_001301645.2:c.346T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004744.5:c.346T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Leber congenital amaurosis 14 (LCA14)
Identifiers:: MONDO: MONDO:0013231; MedGen: C2750063; OMIM: 613341

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521237	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32865313, 29186038, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521237

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (3)
[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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Clinical and molecular findings in a cohort of 152 Brazilian severe early onset inherited retinal dystrophy patients.

Sallum JMF, Motta FL, Arno G, Porto FBO, Resende RG, Belfort R Jr.

Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):728-752. doi: 10.1002/ajmg.c.31828. Epub 2020 Aug 31.

PubMed [citation]

PMID:: 32865313

Molecular Screening of 43 Brazilian Families Diagnosed with Leber Congenital Amaurosis or Early-Onset Severe Retinal Dystrophy.

Porto FBO, Jones EM, Branch J, Soens ZT, Maia IM, Sena IFG, Sampaio SAM, Simões RT, Chen R.

Genes (Basel). 2017 Nov 29;8(12). doi: 10.3390/genes8120355.

PubMed [citation]

PMID:: 29186038
PMCID:: PMC5748673

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV002521237.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.64; 3Cnet: 0.22). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with LRAT related disorder (ClinVar ID: VCV000802098 / PMID: 29186038). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 29186038, 32865313). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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