rs9479298

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.12352-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,592,616 control chromosomes in the GnomAD database, including 453,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48655 hom., cov: 32)

Exomes 𝑓: 0.75 ( 405079 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.10

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P, Orphanet, PanelApp Australia
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
arthrogryposis multiplex congenita 3, myogenic type
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-152337056-T-C is Benign according to our data. Variant chr6-152337056-T-C is described in ClinVar as Benign. ClinVar VariationId is 262158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 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.12352-39A>G		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.12139-39A>G		intron	N/A	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.12352-39A>G	intron	N/A	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.12139-39A>G	intron	N/A	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1	TSL:1	n.5490-39A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120914

AN:

152068

Hom.:

48590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.752

GnomAD2 exomes

AF:

0.748

AC:

168702

AN:

225452

AF XY:

0.740

show subpopulations

Gnomad AFR exome

AF:

0.923

Gnomad AMR exome

AF:

0.698

Gnomad ASJ exome

AF:

0.700

Gnomad EAS exome

AF:

0.856

Gnomad FIN exome

AF:

0.834

Gnomad NFE exome

AF:

0.747

Gnomad OTH exome

AF:

0.742

GnomAD4 exome

AF:

0.748

AC:

1077440

AN:

1440430

Hom.:

405079

Cov.:

AF XY:

0.744

AC XY:

532077

AN XY:

715622

show subpopulations

African (AFR)

AF:

0.922

AC:

30676

AN:

33284

American (AMR)

AF:

0.703

AC:

29810

AN:

42400

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

18092

AN:

25818

East Asian (EAS)

AF:

0.860

AC:

33939

AN:

39456

South Asian (SAS)

AF:

0.623

AC:

52750

AN:

84670

European-Finnish (FIN)

AF:

0.828

AC:

39713

AN:

47968

Middle Eastern (MID)

AF:

0.616

AC:

3503

AN:

5686

European-Non Finnish (NFE)

AF:

0.748

AC:

824424

AN:

1101440

Other (OTH)

AF:

0.746

AC:

44533

AN:

59708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

12630

25261

37891

50522

63152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20186

40372

60558

80744

100930

<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:

0.795

AC:

121041

AN:

152186

Hom.:

48655

Cov.:

AF XY:

0.796

AC XY:

59203

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.919

AC:

38165

AN:

41528

American (AMR)

AF:

0.724

AC:

11071

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2379

AN:

3466

East Asian (EAS)

AF:

0.848

AC:

4389

AN:

5174

South Asian (SAS)

AF:

0.625

AC:

3020

AN:

4834

European-Finnish (FIN)

AF:

0.832

AC:

8808

AN:

10588

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.747

AC:

50787

AN:

68000

Other (OTH)

AF:

0.756

AC:

1590

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1239

2478

3717

4956

6195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.779

Hom.:

9724

Bravo

AF:

0.795

Asia WGS

AF:

0.771

AC:

2684

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Arthrogryposis multiplex congenita 3, myogenic type (1)

Autosomal recessive ataxia, Beauce type (1)

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

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0010

(source)

DANN

Benign

0.40

PhyloP100

-5.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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