NM_001039876.3(SYNE4):c.940C>T (p.His314Tyr) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 2, 2017
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:: RCV000615818.4

Allele description [Variation Report for NM_001039876.3(SYNE4):c.940C>T (p.His314Tyr)]

NM_001039876.3(SYNE4):c.940C>T (p.His314Tyr)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.12

Genomic location:

Preferred name:

NM_001039876.3(SYNE4):c.940C>T (p.His314Tyr)

HGVS:

NC_000019.10:g.36005365G>A
NG_042831.1:g.8429C>T
NM_001039876.3:c.940C>TMANE SELECT
NM_001297735.3:c.601C>T
NP_001034965.1:p.His314Tyr
NP_001284664.1:p.His201Tyr
LRG_1385t1:c.940C>T
LRG_1385:g.8429C>T
LRG_1385p1:p.His314Tyr
NC_000019.9:g.36496267G>A
NM_001039876.1:c.940C>T

Protein change:

H201Y

Links:

dbSNP: rs886101498

NCBI 1000 Genomes Browser:

rs886101498

Molecular consequence:

NM_001039876.3:c.940C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001297735.3:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000731838	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Sep 2, 2017)	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

SCV000731838

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Sep 2, 2017)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000731838.2

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

Description

Variant classified as Uncertain Significance - Favor Benign. The p.His314Tyr var iant in SYNE4 has not been previously reported in individuals with hearing loss, but has been identified in 1/14980 European chromosomes by the Genome Aggregati on Database (gnomAD, http://gnomad.broadinstitute.org). Although this variant ha s been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Histidine (His) at position 314 is not conserved across s pecies and 2 mammals have a Tyrosine (Tyr) at this position. Additional computat ional prediction tools suggest that the p.His314Tyr variant may not impact the p rotein, though this information is not predictive enough to rule out pathogenici ty. In summary, while the clinical significance of the p.His314Tyr variant is un certain, these data suggest that it is more likely to be benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Dec 24, 2022

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