6-152362278-G-T

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.10191C>A(p.Gly3397Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,613,830 control chromosomes in the GnomAD database, including 367,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32077 hom., cov: 32)

Exomes 𝑓: 0.68 ( 335469 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.240

Publications

28 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=-0.54).

BP6

Variant 6-152362278-G-T is Benign according to our data. Variant chr6-152362278-G-T is described in ClinVar as Benign. ClinVar VariationId is 130388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 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.10191C>A	p.Gly3397Gly	synonymous	Exon 64 of 146	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.10212C>A	p.Gly3404Gly	synonymous	Exon 64 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.10191C>A	p.Gly3397Gly	synonymous	Exon 64 of 146	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.10212C>A	p.Gly3404Gly	synonymous	Exon 64 of 146	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1	TSL:1	n.3329C>A		non_coding_transcript_exon	Exon 7 of 19

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98434

AN:

151898

Hom.:

32056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.674

GnomAD2 exomes

AF:

0.659

AC:

165821

AN:

251456

AF XY:

0.658

show subpopulations

Gnomad AFR exome

AF:

0.577

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.670

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.676

AC:

988107

AN:

1461814

Hom.:

335469

Cov.:

AF XY:

0.674

AC XY:

489812

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.574

AC:

19205

AN:

33478

American (AMR)

AF:

0.671

AC:

29997

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

18545

AN:

26136

East Asian (EAS)

AF:

0.822

AC:

32620

AN:

39700

South Asian (SAS)

AF:

0.596

AC:

51449

AN:

86256

European-Finnish (FIN)

AF:

0.607

AC:

32408

AN:

53414

Middle Eastern (MID)

AF:

0.589

AC:

3395

AN:

5768

European-Non Finnish (NFE)

AF:

0.683

AC:

759804

AN:

1111946

Other (OTH)

AF:

0.674

AC:

40684

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

19954

39908

59863

79817

99771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19550

39100

58650

78200

97750

<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:

0.648

AC:

98507

AN:

152016

Hom.:

32077

Cov.:

AF XY:

0.643

AC XY:

47803

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.587

AC:

24324

AN:

41468

American (AMR)

AF:

0.676

AC:

10326

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

2468

AN:

3470

East Asian (EAS)

AF:

0.793

AC:

4087

AN:

5154

South Asian (SAS)

AF:

0.609

AC:

2928

AN:

4810

European-Finnish (FIN)

AF:

0.591

AC:

6228

AN:

10532

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

46034

AN:

67988

Other (OTH)

AF:

0.676

AC:

1425

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1813

3625

5438

7250

9063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.667

Hom.:

131573

Bravo

AF:

0.652

Asia WGS

AF:

0.700

AC:

2437

AN:

3478

EpiCase

AF:

0.669

EpiControl

AF:

0.662

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Autosomal recessive ataxia, Beauce type (2)

Emery-Dreifuss muscular dystrophy 4, autosomal dominant (2)

Arthrogryposis multiplex congenita 3, myogenic type (1)

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.021

(source)

DANN

Benign

0.29

PhyloP100

-0.24

Mutation Taster

=56/44

polymorphism

(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