NM_022787.4(NMNAT1):c.255G>A (p.Trp85Ter) AND Leber congenital amaurosis 9

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 26, 2023
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:: RCV001958992.4

Allele description [Variation Report for NM_022787.4(NMNAT1):c.255G>A (p.Trp85Ter)]

NM_022787.4(NMNAT1):c.255G>A (p.Trp85Ter)

Gene:

NMNAT1:nicotinamide nucleotide adenylyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_022787.4(NMNAT1):c.255G>A (p.Trp85Ter)

HGVS:

NC_000001.11:g.9975731G>A
NG_032954.1:g.37304G>A
NM_001297778.1:c.255G>A
NM_001297779.2:c.255G>A
NM_022787.4:c.255G>AMANE SELECT
NP_001284707.1:p.Trp85Ter
NP_001284708.1:p.Trp85Ter
NP_073624.2:p.Trp85Ter
NC_000001.10:g.10035789G>A

Protein change:

W85*

Links:

dbSNP: rs2101701634

NCBI 1000 Genomes Browser:

rs2101701634

Molecular consequence:

NM_001297778.1:c.255G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001297779.2:c.255G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_022787.4:c.255G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Leber congenital amaurosis 9 (LCA9)
Synonyms:: LCA 9; Amaurosis congenita of Leber, type 9; LCA9 Leber Congenital Amaurosis
Identifiers:: MONDO: MONDO:0012056; MedGen: C1837873; Orphanet: 65; OMIM: 608553

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002242622	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22842229, 22842231, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002242622

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 26, 2023)

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

Citations

PubMed

Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy.

Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, Delphin N, Fares-Taie L, Gerber S, Xerri O, Edelson C, Goldenberg A, Duncombe A, Le Meur G, Hamel C, Silva E, Nitschke P, Calvas P, Munnich A, Roche O, Dollfus H, Kaplan J, et al.

Nat Genet. 2012 Sep;44(9):975-7. doi: 10.1038/ng.2357. Epub 2012 Jul 29.

PubMed [citation]

PMID:: 22842229

Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis.

Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, Yi X, Wu R, Gan H, Shi Y, Chen Y, Barnett C, Wheaton D, Day M, Sutherland J, Heon E, Weleber RG, Gabriel LA, Cong P, Chuang K, Ye S, Sallum JM, et al.

Nat Genet. 2012 Sep;44(9):972-4. doi: 10.1038/ng.2370. Epub 2012 Jul 29.

PubMed [citation]

PMID:: 22842231

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002242622.3

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

Description

This sequence change creates a premature translational stop signal (p.Trp85*) in the NMNAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NMNAT1 are known to be pathogenic (PMID: 22842229). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 22842231). ClinVar contains an entry for this variant (Variation ID: 1459432). For these reasons, this variant has been classified as Pathogenic.

#	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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