rs2252748

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182961.4(SYNE1):c.24825G>A(p.Pro8275Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,613,768 control chromosomes in the GnomAD database, including 72,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7130 hom., cov: 32)

Exomes 𝑓: 0.29 ( 65216 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -3.11

Publications

23 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:

ENSG00000300811 (HGNC:):

ENSG00000300811 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-152148196-C-T is Benign according to our data. Variant chr6-152148196-C-T is described in ClinVar as Benign. ClinVar VariationId is 130427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.24825G>A	p.Pro8275Pro	synonymous_variant	Exon 137 of 146	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 link	c.1290G>A	p.Pro430Pro	synonymous_variant	Exon 8 of 18	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.24825G>A	p.Pro8275Pro	synonymous_variant	Exon 137 of 146	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674.5 link	c.1290G>A	p.Pro430Pro	synonymous_variant	Exon 8 of 18	5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45848

AN:

151942

Hom.:

7124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.331

GnomAD2 exomes

AF:

0.320

AC:

80254

AN:

251104

AF XY:

0.318

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.294

AC:

430304

AN:

1461708

Hom.:

65216

Cov.:

AF XY:

0.297

AC XY:

215936

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.298

AC:

9981

AN:

33476

American (AMR)

AF:

0.466

AC:

20845

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

8814

AN:

26128

East Asian (EAS)

AF:

0.310

AC:

12294

AN:

39698

South Asian (SAS)

AF:

0.396

AC:

34149

AN:

86238

European-Finnish (FIN)

AF:

0.180

AC:

9607

AN:

53414

Middle Eastern (MID)

AF:

0.356

AC:

2051

AN:

5768

European-Non Finnish (NFE)

AF:

0.283

AC:

314365

AN:

1111902

Other (OTH)

AF:

0.301

AC:

18198

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

18030

36060

54090

72120

90150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10710

21420

32130

42840

53550

<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:

0.302

AC:

45889

AN:

152060

Hom.:

7130

Cov.:

AF XY:

0.303

AC XY:

22506

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.304

AC:

12617

AN:

41460

American (AMR)

AF:

0.411

AC:

6284

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1165

AN:

3468

East Asian (EAS)

AF:

0.312

AC:

1606

AN:

5144

South Asian (SAS)

AF:

0.389

AC:

1874

AN:

4820

European-Finnish (FIN)

AF:

0.175

AC:

1854

AN:

10586

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19459

AN:

67994

Other (OTH)

AF:

0.329

AC:

693

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1623

3246

4869

6492

8115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.300

Hom.:

19147

Bravo

AF:

0.322

Asia WGS

AF:

0.337

AC:

1170

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.291

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Mar 09, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 02, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

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 12, 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 12, 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

-0.63

CADD

Benign

0.16

(source)

DANN

Benign

0.71

PhyloP100

-3.1

Mutation Taster

=85/15

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