NM_153026.3(PRICKLE1):c.1621G>T (p.Ala541Ser) AND Epilepsy, progressive myoclonic, 1B

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV000533960.5

Allele description [Variation Report for NM_153026.3(PRICKLE1):c.1621G>T (p.Ala541Ser)]

NM_153026.3(PRICKLE1):c.1621G>T (p.Ala541Ser)

Gene:

PRICKLE1:prickle planar cell polarity protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q12

Genomic location:

Preferred name:

NM_153026.3(PRICKLE1):c.1621G>T (p.Ala541Ser)

HGVS:

NC_000012.12:g.42464413C>A
NG_012965.1:g.130358G>T
NM_001144881.2:c.1621G>T
NM_001144882.2:c.1621G>T
NM_001144883.2:c.1621G>T
NM_153026.3:c.1621G>TMANE SELECT
NP_001138353.1:p.Ala541Ser
NP_001138354.1:p.Ala541Ser
NP_001138355.1:p.Ala541Ser
NP_694571.2:p.Ala541Ser
NC_000012.11:g.42858215C>A
NM_153026.2:c.1621G>T

Protein change:

A541S

Links:

dbSNP: rs763169354

NCBI 1000 Genomes Browser:

rs763169354

Molecular consequence:

NM_001144881.2:c.1621G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144882.2:c.1621G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144883.2:c.1621G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153026.3:c.1621G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Epilepsy, progressive myoclonic, 1B
Synonyms:: Progressive myoclonus epilepsy with ataxia; PME
Identifiers:: MONDO: MONDO:0012904; MedGen: C2676254; Orphanet: 308; OMIM: 612437

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000646875	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31875159, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000646875

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

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

Genetic characteristics of non-familial epilepsy.

Kang KW, Kim W, Cho YW, Lee SK, Jung KY, Shin W, Kim DW, Kim WJ, Lee HW, Kim W, Kim K, Lee SH, Choi SY, Kim MK.

PeerJ. 2019;7:e8278. doi: 10.7717/peerj.8278.

PubMed [citation]

PMID:: 31875159
PMCID:: PMC6925949

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, SCV000646875.3

#	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 alanine with serine at codon 541 of the PRICKLE1 protein (p.Ala541Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs763169354, ExAC 0.02%). This missense change has been observed in individual(s) with epilepsy (PMID: 31875159). 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: "Possibly Damaging"; 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: Feb 7, 2023

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