Variant rs3798756 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.22671C>T(p.Ile7557=) variant causes a synonymous change. The variant allele was found at a frequency of 0.137 in 1,613,848 control chromosomes in the GnomAD database, including 15,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1518 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14467 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.31

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 6-152208125-G-A is Benign according to our data. Variant chr6-152208125-G-A is described in ClinVar as [Benign]. Clinvar id is 130423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152208125-G-A is described in Lovd as [Likely_benign]. Variant chr6-152208125-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.22671C>T	p.Ile7557=	synonymous_variant	125/146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.22671C>T	p.Ile7557=	synonymous_variant	125/146	1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20594

AN:

151910

Hom.:

1516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0848

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.145

AC:

36453

AN:

251110

Hom.:

2997

AF XY:

0.144

AC XY:

19561

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.220

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.0845

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.137

AC:

199824

AN:

1461820

Hom.:

14467

Cov.:

AF XY:

0.137

AC XY:

99691

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0862

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.136

AC:

20613

AN:

152028

Hom.:

1518

Cov.:

AF XY:

0.135

AC XY:

10009

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0848

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.136

Hom.:

2462

Bravo

AF:

0.145

Asia WGS

AF:

0.175

AC:

607

AN:

3478

EpiCase

AF:

0.141

EpiControl

AF:

0.146

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 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. -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 21, 2018	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

-0.23

CADD

Benign

6.5

DANN

Benign

0.92

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