Genetic Variant SYNE1:c.9147-13G>A (chr6-152376571-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.9147-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,611,968 control chromosomes in the GnomAD database, including 182,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19085 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163729 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.559

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-152376571-C-T is Benign according to our data. Variant chr6-152376571-C-T is described in ClinVar as [Benign]. Clinvar id is 262202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152376571-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.9147-13G>A		intron_variant	Intron 57 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.9147-13G>A		intron_variant	Intron 57 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75863

AN:

151736

Hom.:

19064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.508

GnomAD3 exomes

AF:

0.504

AC:

125908

AN:

249794

Hom.:

32323

AF XY:

0.506

AC XY:

68475

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.552

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.458

Gnomad EAS exome

AF:

0.553

Gnomad SAS exome

AF:

0.598

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.471

AC:

687474

AN:

1460114

Hom.:

163729

Cov.:

AF XY:

0.475

AC XY:

344916

AN XY:

726414

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.503

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.595

Gnomad4 FIN exome

AF:

0.513

Gnomad4 NFE exome

AF:

0.452

Gnomad4 OTH exome

AF:

0.484

GnomAD4 genome

AF:

0.500

AC:

75928

AN:

151854

Hom.:

19085

Cov.:

AF XY:

0.504

AC XY:

37380

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.548

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.470

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.582

Gnomad4 FIN

AF:

0.524

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.471

Hom.:

36380

Bravo

AF:

0.498

Asia WGS

AF:

0.526

AC:

1828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 25, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Benign:2

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 15, 2021

Genome-Nilou Lab

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

- -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

-0.87

CADD

Benign

DANN

Benign

0.48

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