rs58905396

Variant summary

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

The NM_182961.4(SYNE1):c.8163C>T(p.Ser2721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 1,613,880 control chromosomes in the GnomAD database, including 1,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 653 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 612 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.94

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=-0.56).

BP6

Variant 6-152390294-G-A is Benign according to our data. Variant chr6-152390294-G-A is described in ClinVar as [Benign]. Clinvar id is 130449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152390294-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.8163C>T	p.Ser2721=	synonymous_variant	53/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.8163C>T	p.Ser2721=	synonymous_variant	53/146	1	NM_182961.4	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.8184C>T	p.Ser2728=	synonymous_variant	53/146	1
SYNE1	ENST00000461872.6 linkuse as main transcript	n.8381C>T		non_coding_transcript_exon_variant	51/55	1

Frequencies

GnomAD3 genomes

AF:

0.0511

AC:

7763

AN:

152046

Hom.:

650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0135

AC:

3389

AN:

251234

Hom.:

303

AF XY:

0.00965

AC XY:

1310

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.00821

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00542

AC:

7916

AN:

1461716

Hom.:

612

Cov.:

AF XY:

0.00473

AC XY:

3441

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000479

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0512

AC:

7792

AN:

152164

Hom.:

653

Cov.:

AF XY:

0.0500

AC XY:

3722

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.0209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0230

Hom.:

137

Bravo

AF:

0.0596

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 22, 2019

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

Cadd

Benign

1.2

Dann

Benign

0.66

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