Variant rs149670417 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_182961.4(SYNE1):c.1983C>T(p.Asn661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,613,562 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 21 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.00500

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 6-152463467-G-A is Benign according to our data. Variant chr6-152463467-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 194991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152463467-G-A is described in Lovd as [Likely_benign]. Variant chr6-152463467-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.005 with no splicing effect.

BS2

High AC in GnomAd4 at 554 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.1983C>T	p.Asn661=	synonymous_variant	19/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.1983C>T	p.Asn661=	synonymous_variant	19/146	1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

554

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00645

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00314

AC:

789

AN:

250938

Hom.:

AF XY:

0.00301

AC XY:

408

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.00562

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00554

AC:

8097

AN:

1461414

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

3894

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00406

Gnomad4 NFE exome

AF:

0.00683

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.00364

AC:

554

AN:

152148

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

228

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00255

Gnomad4 NFE

AF:

0.00646

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00457

Hom.:

Bravo

AF:

0.00323

EpiCase

AF:

0.00425

EpiControl

AF:

0.00504

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SYNE1: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 29, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 02, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely 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

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.56

DANN

Benign

0.72

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