rs117184249

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182961.4(SYNE1):c.6889G>A(p.Gly2297Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000578 in 1,614,040 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 6 hom. )

Consequence

SYNE1
NM_182961.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.98

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

Computational evidence support a benign effect (MetaRNN=0.0055975616).

BP6

Variant 6-152401278-C-T is Benign according to our data. Variant chr6-152401278-C-T is described in ClinVar as Benign. ClinVar VariationId is 355917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000577 (844/1461782) while in subpopulation EAS AF = 0.0167 (661/39684). AF 95% confidence interval is 0.0156. There are 6 homozygotes in GnomAdExome4. There are 420 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AD,AR gene

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.6889G>A	p.Gly2297Arg	missense	Exon 47 of 146	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.6910G>A	p.Gly2304Arg	missense	Exon 47 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.6889G>A	p.Gly2297Arg	missense	Exon 47 of 146	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.6910G>A	p.Gly2304Arg	missense	Exon 47 of 146	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000461872.6	TSL:1	n.7107G>A		non_coding_transcript_exon	Exon 45 of 55

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000931

AC:

234

AN:

251262

AF XY:

0.000861

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000577

AC:

844

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

420

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0167

AC:

661

AN:

39684

South Asian (SAS)

AF:

0.000243

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000120

AC:

133

AN:

1111990

Other (OTH)

AF:

0.000431

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000585

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41560

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0150

AC:

AN:

5184

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000422

Hom.:

Bravo

AF:

0.000797

ExAC

AF:

0.000931

AC:

113

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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)

SYNE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

5.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.2

REVEL

Benign

0.096

Sift

Benign

0.17

Sift4G

Benign

0.26

Polyphen

0.68

Vest4

0.31

MutPred

0.33

Gain of MoRF binding (P = 0.0489)

MVP

0.41

MPC

0.16

ClinPred

0.035

GERP RS

5.3

Varity_R

0.24

gMVP

0.23

Mutation Taster

=80/20

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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