6-152308496-C-T

Variant names:

Variant summary

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

The NM_182961.4(SYNE1):c.17339G>A(p.Arg5780Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,614,034 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 95 hom., cov: 31)

Exomes 𝑓: 0.011 ( 254 hom. )

Consequence

SYNE1
NM_182961.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.29

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 (MetaRNN=0.0018066168).

BP6

Variant 6-152308496-C-T is Benign according to our data. Variant chr6-152308496-C-T is described in ClinVar as [Benign]. Clinvar id is 130411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152308496-C-T is described in Lovd as [Benign]. Variant chr6-152308496-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.17339G>A	p.Arg5780Gln	missense_variant	Exon 91 of 146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 link	c.17339G>A	p.Arg5780Gln	missense_variant	Exon 91 of 146	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 link	c.17126G>A	p.Arg5709Gln	missense_variant	Exon 90 of 146	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000367256.9 link	n.1031G>A		non_coding_transcript_exon_variant	Exon 6 of 61	1
SYNE1	ENST00000409694.6 link	n.923G>A		non_coding_transcript_exon_variant	Exon 4 of 59	1

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4061

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.0392

Gnomad SAS

AF:

0.0349

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00662

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0195

AC:

4914

AN:

251464

Hom.:

101

AF XY:

0.0192

AC XY:

2616

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0581

Gnomad AMR exome

AF:

0.0261

Gnomad ASJ exome

AF:

0.0313

Gnomad EAS exome

AF:

0.0394

Gnomad SAS exome

AF:

0.0362

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00669

Gnomad OTH exome

AF:

0.0173

GnomAD4 exome

AF:

0.0105

AC:

15414

AN:

1461856

Hom.:

254

Cov.:

AF XY:

0.0113

AC XY:

8229

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0572

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.0296

Gnomad4 SAS exome

AF:

0.0363

Gnomad4 FIN exome

AF:

0.00247

Gnomad4 NFE exome

AF:

0.00519

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0268

AC:

4077

AN:

152178

Hom.:

Cov.:

AF XY:

0.0275

AC XY:

2048

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0597

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0309

Gnomad4 EAS

AF:

0.0389

Gnomad4 SAS

AF:

0.0341

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00665

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0308

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.0626

AC:

276

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.0196

AC:

2379

Asia WGS

AF:

0.0410

AC:

141

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00788

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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. -

Feb 18, 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;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 13, 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 13, 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

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.018

Sift

Benign

0.062

T;.;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.38

B;.;.

Vest4

0.14

MPC

0.59

ClinPred

0.036

GERP RS

3.2

Varity_R

0.060

gMVP

0.11

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