NM_182961.4(SYNE1):c.24779C>T (p.Ser8260Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 10, 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:: RCV001040210.7

Allele description [Variation Report for NM_182961.4(SYNE1):c.24779C>T (p.Ser8260Leu)]

NM_182961.4(SYNE1):c.24779C>T (p.Ser8260Leu)

Gene:

SYNE1:spectrin repeat containing nuclear envelope protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q25.2

Genomic location:

Preferred name:

NM_182961.4(SYNE1):c.24779C>T (p.Ser8260Leu)

HGVS:

NC_000006.12:g.152148242G>A
NG_012855.2:g.494158C>T
NM_001347701.2:c.1385C>T
NM_001347702.2:c.1244C>T
NM_033071.5:c.24566C>T
NM_182961.4:c.24779C>TMANE SELECT
NP_001334630.1:p.Ser462Leu
NP_001334631.1:p.Ser415Leu
NP_149062.1:p.Ser8189Leu
NP_149062.2:p.Ser8189Leu
NP_892006.3:p.Ser8260Leu
LRG_427t1:c.24779C>T
LRG_427t2:c.24566C>T
LRG_427:g.494158C>T
LRG_427p1:p.Ser8260Leu
LRG_427p2:p.Ser8189Leu
NC_000006.11:g.152469377G>A
NM_033071.3:c.24566C>T

Protein change:

S415L

Links:

dbSNP: rs188852595

NCBI 1000 Genomes Browser:

rs188852595

Molecular consequence:

NM_001347701.2:c.1385C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001347702.2:c.1244C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033071.5:c.24566C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_182961.4:c.24779C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive ataxia, Beauce type
Synonyms:: ATAXIA, RECESSIVE, OF BEAUCE; Spinocerebellar ataxia, autosomal recessive 8; SYNE1-Related Autosomal Recessive Cerebellar Ataxia
Identifiers:: MONDO: MONDO:0012549; MedGen: C1853116; Orphanet: 88644; OMIM: 610743

Name:: Emery-Dreifuss muscular dystrophy 4, autosomal dominant (EDMD4)
Synonyms:: EMERY-DREIFUSS MUSCULAR DYSTROPHY 4 WITH VARIABLE FEATURES
Identifiers:: MONDO: MONDO:0013071; MedGen: C2751807; Orphanet: 261; OMIM: 612998

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001203771	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 10, 2023)	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

SCV001203771

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 10, 2023)

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, SCV001203771.5

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

Description

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 838625). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is present in population databases (rs188852595, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 8189 of the SYNE1 protein (p.Ser8189Leu).

#	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

ClinVar

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