rs10499268

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_182961.4(SYNE1):c.13221C>T(p.Asp4407Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,614,068 control chromosomes in the GnomAD database, including 1,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 99 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1381 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.350

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 6-152331464-G-A is Benign according to our data. Variant chr6-152331464-G-A is described in ClinVar as Benign. ClinVar VariationId is 130403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.35 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0343 (5227/152204) while in subpopulation SAS AF = 0.0473 (228/4818). AF 95% confidence interval is 0.0423. There are 99 homozygotes in GnomAd4. There are 2472 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 99 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.13221C>T	p.Asp4407Asp	synonymous_variant	Exon 78 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 link	c.13221C>T	p.Asp4407Asp	synonymous_variant	Exon 78 of 146	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 link	c.13008C>T	p.Asp4336Asp	synonymous_variant	Exon 77 of 146	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000490135.6 link	n.567C>T		non_coding_transcript_exon_variant	Exon 2 of 11	1

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5217

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.0471

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0312

GnomAD2 exomes

AF:

0.0332

AC:

8352

AN:

251336

AF XY:

0.0348

show subpopulations

Gnomad AFR exome

AF:

0.0297

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0438

Gnomad EAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0414

AC:

60553

AN:

1461864

Hom.:

1381

Cov.:

AF XY:

0.0410

AC XY:

29815

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0305

AC:

1021

AN:

33480

American (AMR)

AF:

0.0164

AC:

732

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0433

AC:

1131

AN:

26136

East Asian (EAS)

AF:

0.0220

AC:

875

AN:

39700

South Asian (SAS)

AF:

0.0435

AC:

3751

AN:

86252

European-Finnish (FIN)

AF:

0.0152

AC:

810

AN:

53416

Middle Eastern (MID)

AF:

0.0217

AC:

125

AN:

5768

European-Non Finnish (NFE)

AF:

0.0446

AC:

49639

AN:

1111998

Other (OTH)

AF:

0.0409

AC:

2469

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

4105

8210

12314

16419

20524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1908

3816

5724

7632

9540

<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:

0.0343

AC:

5227

AN:

152204

Hom.:

Cov.:

AF XY:

0.0332

AC XY:

2472

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0304

AC:

1264

AN:

41526

American (AMR)

AF:

0.0194

AC:

297

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0418

AC:

145

AN:

3470

East Asian (EAS)

AF:

0.0201

AC:

104

AN:

5178

South Asian (SAS)

AF:

0.0473

AC:

228

AN:

4818

European-Finnish (FIN)

AF:

0.0144

AC:

153

AN:

10590

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0423

AC:

2875

AN:

68020

Other (OTH)

AF:

0.0308

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

253

505

758

1010

1263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0382

Hom.:

219

Bravo

AF:

0.0342

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

EpiCase

AF:

0.0407

EpiControl

AF:

0.0409

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

- -

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. -

Feb 29, 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. -

Clinical Genetics, Academic Medical Center

Significance: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 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

-0.57

CADD

Benign

0.19

(source)

DANN

Benign

0.42

PhyloP100

-0.35

Mutation Taster

=99/1

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