rs12664753

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182961.4(SYNE1):c.17745C>T(p.His5915=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,740 control chromosomes in the GnomAD database, including 30,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2201 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28012 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.284

Variant links:

Genes affected

SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SYNE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-152294065-G-A is Benign according to our data. Variant chr6-152294065-G-A is described in ClinVar as [Benign]. Clinvar id is 130414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152294065-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.284 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.17745C>T	p.His5915=	synonymous_variant	94/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.17745C>T	p.His5915=	synonymous_variant	94/146	1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22850

AN:

152016

Hom.:

2203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.138

GnomAD3 exomes

AF:

0.190

AC:

47774

AN:

251352

Hom.:

5009

AF XY:

0.192

AC XY:

26115

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0339

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.191

AC:

279614

AN:

1461606

Hom.:

28012

Cov.:

AF XY:

0.192

AC XY:

139472

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0296

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.150

AC:

22846

AN:

152134

Hom.:

2201

Cov.:

AF XY:

0.154

AC XY:

11480

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.168

Hom.:

2784

Bravo

AF:

0.140

Asia WGS

AF:

0.168

AC:

584

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.184

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 05, 2017	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 02, 2018

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.28

DANN

Benign

0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over