chr6-152325144-G-C

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.15597C>G(p.Ala5199Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,614,070 control chromosomes in the GnomAD database, including 1,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 174 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1372 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0140

Publications

13 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet, PanelApp Australia, G2P
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
arthrogryposis multiplex congenita 3, myogenic type
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
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=-0.5).

BP6

Variant 6-152325144-G-C is Benign according to our data. Variant chr6-152325144-G-C is described in ClinVar as Benign. ClinVar VariationId is 130409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.15597C>G	p.Ala5199Ala	synonymous	Exon 81 of 146	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.15384C>G	p.Ala5128Ala	synonymous	Exon 80 of 146	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.15597C>G	p.Ala5199Ala	synonymous	Exon 81 of 146	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.15384C>G	p.Ala5128Ala	synonymous	Exon 80 of 146	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000490135.6	TSL:1	n.2943C>G		non_coding_transcript_exon	Exon 5 of 11

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6271

AN:

152064

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0320

Gnomad OTH

AF:

0.0378

GnomAD2 exomes

AF:

0.0450

AC:

11327

AN:

251436

AF XY:

0.0432

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.0516

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0307

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0360

AC:

52600

AN:

1461888

Hom.:

1372

Cov.:

AF XY:

0.0356

AC XY:

25881

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0513

AC:

1717

AN:

33480

American (AMR)

AF:

0.0521

AC:

2328

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0155

AC:

405

AN:

26136

East Asian (EAS)

AF:

0.152

AC:

6035

AN:

39700

South Asian (SAS)

AF:

0.0344

AC:

2966

AN:

86258

European-Finnish (FIN)

AF:

0.0370

AC:

1976

AN:

53418

Middle Eastern (MID)

AF:

0.0338

AC:

195

AN:

5766

European-Non Finnish (NFE)

AF:

0.0311

AC:

34595

AN:

1112012

Other (OTH)

AF:

0.0395

AC:

2383

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3214

6428

9642

12856

16070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1442

2884

4326

5768

7210

<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:

0.0413

AC:

6280

AN:

152182

Hom.:

174

Cov.:

AF XY:

0.0417

AC XY:

3101

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0517

AC:

2148

AN:

41524

American (AMR)

AF:

0.0339

AC:

519

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3468

East Asian (EAS)

AF:

0.149

AC:

770

AN:

5160

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4824

European-Finnish (FIN)

AF:

0.0323

AC:

343

AN:

10604

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0320

AC:

2173

AN:

67990

Other (OTH)

AF:

0.0379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

287

574

862

1149

1436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0302

Hom.:

Bravo

AF:

0.0427

Asia WGS

AF:

0.0840

AC:

293

AN:

3478

EpiCase

AF:

0.0298

EpiControl

AF:

0.0283

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Autosomal recessive ataxia, Beauce type (1)

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.1

(source)

DANN

Benign

0.77

PhyloP100

0.014

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over