ENST00000409694.6:n.270C>T

Variant names:

Variant summary

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

The ENST00000409694.6(SYNE1):n.270C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,608,712 control chromosomes in the GnomAD database, including 1,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 106 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1079 hom. )

Consequence

SYNE1
ENST00000409694.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.959

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: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
arthrogryposis multiplex congenita 3, myogenic type
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
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=-0.79).

BP6

Variant 6-152310898-G-A is Benign according to our data. Variant chr6-152310898-G-A is described in ClinVar as Benign. ClinVar VariationId is 262170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.16711-25C>T		intron_variant	Intron 87 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.16711-25C>T		intron_variant	Intron 87 of 145	1	NM_182961.4	ENSP00000356224.5

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4160

AN:

152114

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.0422

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0205

GnomAD2 exomes

AF:

0.0369

AC:

9035

AN:

244862

AF XY:

0.0354

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.0460

Gnomad ASJ exome

AF:

0.00484

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.0429

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0304

AC:

44345

AN:

1456480

Hom.:

1079

Cov.:

AF XY:

0.0297

AC XY:

21553

AN XY:

724494

show subpopulations

African (AFR)

AF:

0.0107

AC:

358

AN:

33404

American (AMR)

AF:

0.0449

AC:

1992

AN:

44344

Ashkenazi Jewish (ASJ)

AF:

0.00484

AC:

126

AN:

26050

East Asian (EAS)

AF:

0.151

AC:

6008

AN:

39660

South Asian (SAS)

AF:

0.0178

AC:

1520

AN:

85620

European-Finnish (FIN)

AF:

0.0425

AC:

2236

AN:

52642

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0273

AC:

30251

AN:

1108822

Other (OTH)

AF:

0.0304

AC:

1832

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2214

4427

6641

8854

11068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1244

2488

3732

4976

6220

<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:

0.0273

AC:

4162

AN:

152232

Hom.:

106

Cov.:

AF XY:

0.0282

AC XY:

2097

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0132

AC:

548

AN:

41542

American (AMR)

AF:

0.0269

AC:

411

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.135

AC:

699

AN:

5172

South Asian (SAS)

AF:

0.0263

AC:

127

AN:

4824

European-Finnish (FIN)

AF:

0.0422

AC:

448

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0274

AC:

1861

AN:

68010

Other (OTH)

AF:

0.0208

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

210

419

629

838

1048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0242

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.0790

AC:

272

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

(source)

DANN

Benign

0.68

PhyloP100

0.96

BranchPoint Hunter

2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over