NM_198586.3(NHLRC1):c.307G>T (p.Ala103Ser) AND Lafora disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 25, 2021
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:: RCV000558033.5

Allele description [Variation Report for NM_198586.3(NHLRC1):c.307G>T (p.Ala103Ser)]

NM_198586.3(NHLRC1):c.307G>T (p.Ala103Ser)

Gene:

NHLRC1:NHL repeat containing E3 ubiquitin protein ligase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p22.3

Genomic location:

Preferred name:

NM_198586.3(NHLRC1):c.307G>T (p.Ala103Ser)

HGVS:

NC_000006.12:g.18122300C>A
NG_016750.1:g.5321G>T
NM_198586.3:c.307G>TMANE SELECT
NP_940988.2:p.Ala103Ser
NC_000006.11:g.18122531C>A
NM_198586.2:c.307G>T

Protein change:

A103S

Links:

dbSNP: rs568131096

NCBI 1000 Genomes Browser:

rs568131096

Molecular consequence:

NM_198586.3:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lafora disease
Synonyms:: Lafora body disorder; Myoclonic epilepsy of Lafora; Epilepsy progressive myoclonic 2
Identifiers:: MONDO: MONDO:0009697; MedGen: C0751783; Orphanet: 501; OMIM: PS254780

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000636488	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 25, 2021)	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

SCV000636488

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 25, 2021)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000636488.5

#	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 alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 103 of the NHLRC1 protein (p.Ala103Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with NHLRC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 462939). 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: "Benign"; 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: Mar 16, 2024

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