rs2252748

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182961.4(SYNE1):c.24825G>A(p.Pro8275Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,613,768 control chromosomes in the GnomAD database, including 72,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7130 hom., cov: 32)

Exomes 𝑓: 0.29 ( 65216 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -3.11

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-152148196-C-T is Benign according to our data. Variant chr6-152148196-C-T is described in ClinVar as [Benign]. Clinvar id is 130427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152148196-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.24825G>A	p.Pro8275Pro	synonymous_variant	Exon 137 of 146	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 link	c.1290G>A	p.Pro430Pro	synonymous_variant	Exon 8 of 18	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.24825G>A	p.Pro8275Pro	synonymous_variant	Exon 137 of 146	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674.5 link	c.1290G>A	p.Pro430Pro	synonymous_variant	Exon 8 of 18	5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45848

AN:

151942

Hom.:

7124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.320

AC:

80254

AN:

251104

Hom.:

13895

AF XY:

0.318

AC XY:

43165

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.301

Gnomad SAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.294

AC:

430304

AN:

1461708

Hom.:

65216

Cov.:

AF XY:

0.297

AC XY:

215936

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.302

AC:

45889

AN:

152060

Hom.:

7130

Cov.:

AF XY:

0.303

AC XY:

22506

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.304

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.336

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.296

Hom.:

12151

Bravo

AF:

0.322

Asia WGS

AF:

0.337

AC:

1170

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.291

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 09, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 02, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.16

DANN

Benign

0.71

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over