rs3798756

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.22671C>T(p.Ile7557Ile) 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

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive ataxia, Beauce type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
arthrogryposis multiplex congenita 3, myogenic type
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
autosomal dominant Emery-Dreifuss muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive myogenic arthrogryposis multiplex congenita
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SYNE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 130423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.22671C>T	p.Ile7557Ile	synonymous_variant	Exon 125 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.22671C>T	p.Ile7557Ile	synonymous_variant	Exon 125 of 146	1	NM_182961.4	ENSP00000356224.5		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

GnomAD2 exomes

AF:

0.145

AC:

36453

AN:

251110

AF XY:

0.144

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 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

African (AFR)

AF:

0.120

AC:

4019

AN:

33480

American (AMR)

AF:

0.202

AC:

9033

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3559

AN:

26136

East Asian (EAS)

AF:

0.235

AC:

9344

AN:

39686

South Asian (SAS)

AF:

0.150

AC:

12935

AN:

86256

European-Finnish (FIN)

AF:

0.0862

AC:

4601

AN:

53404

Middle Eastern (MID)

AF:

0.192

AC:

1109

AN:

5768

European-Non Finnish (NFE)

AF:

0.132

AC:

146583

AN:

1111974

Other (OTH)

AF:

0.143

AC:

8641

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11048

22095

33143

44190

55238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5410

10820

16230

21640

27050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.136

AC:

20613

AN:

152028

Hom.:

1518

Cov.:

AF XY:

0.135

AC XY:

10009

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.121

AC:

5009

AN:

41454

American (AMR)

AF:

0.190

AC:

2895

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

499

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1145

AN:

5148

South Asian (SAS)

AF:

0.149

AC:

717

AN:

4800

European-Finnish (FIN)

AF:

0.0848

AC:

897

AN:

10584

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8951

AN:

67984

Other (OTH)

AF:

0.147

AC:

310

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

875

1749

2624

3498

4373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

5121

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

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Jan 07, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 28, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 21, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

6.5

(source)

DANN

Benign

0.92

PhyloP100

4.3

Mutation Taster

=57/43

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over