rs12662994

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.17202+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,612,526 control chromosomes in the GnomAD database, including 10,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 1032 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9323 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.03

Publications

6 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

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-152309811-C-T is Benign according to our data. Variant chr6-152309811-C-T is described in ClinVar as Benign. ClinVar VariationId is 262171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 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.17202+24G>A		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.16989+24G>A		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.17202+24G>A	intron	N/A	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.16993+20G>A	intron	N/A	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000367256.9	TSL:1	n.894+24G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0977

AC:

14857

AN:

152130

Hom.:

1038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0856

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.132

AC:

33061

AN:

250328

AF XY:

0.127

show subpopulations

Gnomad AFR exome

AF:

0.0449

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0894

Gnomad FIN exome

AF:

0.0782

Gnomad NFE exome

AF:

0.0957

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.101

AC:

147696

AN:

1460276

Hom.:

9323

Cov.:

AF XY:

0.102

AC XY:

73965

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.0444

AC:

1487

AN:

33462

American (AMR)

AF:

0.322

AC:

14397

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4070

AN:

26126

East Asian (EAS)

AF:

0.116

AC:

4601

AN:

39698

South Asian (SAS)

AF:

0.145

AC:

12534

AN:

86180

European-Finnish (FIN)

AF:

0.0796

AC:

4178

AN:

52478

Middle Eastern (MID)

AF:

0.145

AC:

793

AN:

5470

European-Non Finnish (NFE)

AF:

0.0892

AC:

99160

AN:

1111818

Other (OTH)

AF:

0.107

AC:

6476

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6443

12885

19328

25770

32213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3786

7572

11358

15144

18930

<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:

0.0976

AC:

14861

AN:

152250

Hom.:

1032

Cov.:

AF XY:

0.101

AC XY:

7538

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0472

AC:

1961

AN:

41568

American (AMR)

AF:

0.239

AC:

3657

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3472

East Asian (EAS)

AF:

0.101

AC:

523

AN:

5178

South Asian (SAS)

AF:

0.134

AC:

647

AN:

4816

European-Finnish (FIN)

AF:

0.0856

AC:

908

AN:

10606

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0927

AC:

6304

AN:

68016

Other (OTH)

AF:

0.128

AC:

270

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

654

1308

1961

2615

3269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.108

Hom.:

928

Bravo

AF:

0.109

Asia WGS

AF:

0.132

AC:

457

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Arthrogryposis multiplex congenita 3, myogenic type (1)

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

-0.80

CADD

Benign

2.7

(source)

DANN

Benign

0.57

PhyloP100

-1.0

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