NM_001039876.3(SYNE4):c.662_666del (p.Glu221fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 17, 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:: RCV003840912.2

Allele description [Variation Report for NM_001039876.3(SYNE4):c.662_666del (p.Glu221fs)]

NM_001039876.3(SYNE4):c.662_666del (p.Glu221fs)

Gene:

SYNE4:spectrin repeat containing nuclear envelope family member 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q13.12

Genomic location:

Preferred name:

NM_001039876.3(SYNE4):c.662_666del (p.Glu221fs)

HGVS:

NC_000019.10:g.36006624_36006628del
NG_042831.1:g.7166_7170del
NM_001039876.3:c.662_666delMANE SELECT
NM_001297735.3:c.323_327del
NP_001034965.1:p.Glu221fs
NP_001284664.1:p.Glu108fs
LRG_1385t1:c.662_666del
LRG_1385:g.7166_7170del
LRG_1385p1:p.Glu221fs
NC_000019.9:g.36497526_36497530del

Protein change:

E108fs

Molecular consequence:

NM_001039876.3:c.662_666del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001297735.3:c.323_327del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004642882	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23348741, 28958982, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004642882

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 17, 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

The LINC complex is essential for hearing.

Horn HF, Brownstein Z, Lenz DR, Shivatzki S, Dror AA, Dagan-Rosenfeld O, Friedman LM, Roux KJ, Kozlov S, Jeang KT, Frydman M, Burke B, Stewart CL, Avraham KB.

J Clin Invest. 2013 Feb;123(2):740-50. doi: 10.1172/JCI66911. Epub 2013 Jan 25.

PubMed [citation]

PMID:: 23348741
PMCID:: PMC3561815

A Novel Variant in SYNE4 Confirms its Causative Role in Sensorineural Hearing Loss.

Masterson J, Yıldırım B, Gökkaya E, Tokgöz Yılmaz S, Tekin M.

Balkan Med J. 2018 Mar 15;35(2):196-198. doi: 10.4274/balkanmedj.2017.0946. Epub 2017 Sep 29.

PubMed [citation]

PMID:: 28958982
PMCID:: PMC5863260

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004642882.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with SYNE4-related conditions. This variant is present in population databases (rs772404105, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Glu221Glyfs*18) in the SYNE4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNE4 are known to be pathogenic (PMID: 23348741, 28958982).

#	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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