rs17082701

Variant summary

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

The NM_182961.4(SYNE1):c.3306C>T(p.His1102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,614,018 control chromosomes in the GnomAD database, including 3,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 374 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2802 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.484

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=-0.83).

BP6

Variant 6-152450714-G-A is Benign according to our data. Variant chr6-152450714-G-A is described in ClinVar as [Benign]. Clinvar id is 130439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152450714-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.484 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 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.3306C>T	p.His1102=	synonymous_variant	27/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.3306C>T	p.His1102=	synonymous_variant	27/146	1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0645

AC:

9808

AN:

152046

Hom.:

371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0583

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0458

Gnomad FIN

AF:

0.0532

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0678

Gnomad OTH

AF:

0.0756

GnomAD3 exomes

AF:

0.0562

AC:

14130

AN:

251460

Hom.:

569

AF XY:

0.0570

AC XY:

7753

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0752

Gnomad AMR exome

AF:

0.0354

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.000979

Gnomad SAS exome

AF:

0.0457

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0665

Gnomad OTH exome

AF:

0.0614

GnomAD4 exome

AF:

0.0595

AC:

87031

AN:

1461854

Hom.:

2802

Cov.:

AF XY:

0.0594

AC XY:

43181

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0762

Gnomad4 AMR exome

AF:

0.0379

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0456

Gnomad4 FIN exome

AF:

0.0543

Gnomad4 NFE exome

AF:

0.0621

Gnomad4 OTH exome

AF:

0.0615

GnomAD4 genome

AF:

0.0646

AC:

9824

AN:

152164

Hom.:

374

Cov.:

AF XY:

0.0630

AC XY:

4685

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0722

Gnomad4 AMR

AF:

0.0583

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0456

Gnomad4 FIN

AF:

0.0532

Gnomad4 NFE

AF:

0.0678

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.0686

Hom.:

479

Bravo

AF:

0.0644

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

EpiCase

AF:

0.0678

EpiControl

AF:

0.0679

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 02, 2018

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

1.9

Dann

Benign

0.37

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