chr6-152352384-A-C

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.11254-31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,599,144 control chromosomes in the GnomAD database, including 289,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.58 ( 25233 hom., cov: 30)

Exomes 𝑓: 0.60 ( 264380 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.349

Publications

8 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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-152352384-A-C is Benign according to our data. Variant chr6-152352384-A-C is described in ClinVar as Benign. ClinVar VariationId is 262153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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.11254-31T>G		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.11209-31T>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.11254-31T>G	intron	N/A	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.11209-31T>G	intron	N/A	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1	TSL:1	n.4392-31T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87102

AN:

151274

Hom.:

25216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.591

GnomAD2 exomes

AF:

0.583

AC:

142089

AN:

243540

AF XY:

0.582

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.644

Gnomad EAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.603

AC:

873439

AN:

1447762

Hom.:

264380

Cov.:

AF XY:

0.601

AC XY:

432844

AN XY:

720434

show subpopulations

African (AFR)

AF:

0.499

AC:

16372

AN:

32794

American (AMR)

AF:

0.601

AC:

26147

AN:

43494

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

16728

AN:

25874

East Asian (EAS)

AF:

0.639

AC:

25331

AN:

39626

South Asian (SAS)

AF:

0.523

AC:

44057

AN:

84196

European-Finnish (FIN)

AF:

0.545

AC:

28840

AN:

52874

Middle Eastern (MID)

AF:

0.513

AC:

2927

AN:

5710

European-Non Finnish (NFE)

AF:

0.614

AC:

677338

AN:

1103326

Other (OTH)

AF:

0.596

AC:

35699

AN:

59868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

17003

34006

51010

68013

85016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18314

36628

54942

73256

91570

<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:

0.576

AC:

87161

AN:

151382

Hom.:

25233

Cov.:

AF XY:

0.572

AC XY:

42273

AN XY:

73910

show subpopulations

African (AFR)

AF:

0.512

AC:

21142

AN:

41254

American (AMR)

AF:

0.613

AC:

9337

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2222

AN:

3468

East Asian (EAS)

AF:

0.619

AC:

3178

AN:

5130

South Asian (SAS)

AF:

0.535

AC:

2568

AN:

4798

European-Finnish (FIN)

AF:

0.531

AC:

5464

AN:

10294

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.609

AC:

41341

AN:

67880

Other (OTH)

AF:

0.593

AC:

1249

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1848

3697

5545

7394

9242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.537

Hom.:

3480

Bravo

AF:

0.580

Asia WGS

AF:

0.594

AC:

2069

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

-0.90

CADD

Benign

0.90

(source)

DANN

Benign

0.29

PhyloP100

-0.35

BranchPoint Hunter

0.0

Mutation Taster

=100/0

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