dbSNP rs9322361: SYNE1:c.25459-1190T>C (chr6-152138008-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182961.4(SYNE1):c.25459-1190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,126 control chromosomes in the GnomAD database, including 1,297 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1297 hom., cov: 32)

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

Publications

5 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:

ENSG00000300811 (HGNC:):

ENSG00000300811 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.25459-1190T>C		intron_variant	Intron 140 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 link	c.1993-1190T>C		intron_variant	Intron 12 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.25459-1190T>C		intron_variant	Intron 140 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5 link	c.1993-1190T>C		intron_variant	Intron 12 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17581

AN:

152008

Hom.:

1299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.0289

Gnomad SAS

AF:

0.0512

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.115

AC:

17569

AN:

152126

Hom.:

1297

Cov.:

AF XY:

0.114

AC XY:

8498

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0315

AC:

1308

AN:

41502

American (AMR)

AF:

0.114

AC:

1747

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

504

AN:

3466

East Asian (EAS)

AF:

0.0287

AC:

149

AN:

5186

South Asian (SAS)

AF:

0.0504

AC:

242

AN:

4802

European-Finnish (FIN)

AF:

0.179

AC:

1895

AN:

10582

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11311

AN:

67988

Other (OTH)

AF:

0.128

AC:

269

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

787

1575

2362

3150

3937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.149

Hom.:

3880

Bravo

AF:

0.108

Asia WGS

AF:

0.0510

AC:

180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.3

(source)

DANN

Benign

0.79

PhyloP100

0.97

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over