rs71575926

Positions:

chr6-152339316-G-A

Variant summary

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

The NM_182961.4(SYNE1):c.12276C>T(p.Leu4092=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,613,840 control chromosomes in the GnomAD database, including 14,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1300 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13562 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0800

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=-0.51).

BP6

Variant 6-152339316-G-A is Benign according to our data. Variant chr6-152339316-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 130398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152339316-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 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.12276C>T	p.Leu4092=	synonymous_variant	75/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.12276C>T	p.Leu4092=	synonymous_variant	75/146	1	NM_182961.4	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.12063C>T	p.Leu4021=	synonymous_variant	74/146	1
SYNE1	ENST00000471834.1 linkuse as main transcript	n.5414C>T		non_coding_transcript_exon_variant	18/19	1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18195

AN:

152152

Hom.:

1300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0886

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.0790

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0321

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.0884

GnomAD3 exomes

AF:

0.113

AC:

28415

AN:

251412

Hom.:

2137

AF XY:

0.112

AC XY:

15263

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0891

Gnomad AMR exome

AF:

0.0558

Gnomad ASJ exome

AF:

0.0470

Gnomad EAS exome

AF:

0.0306

Gnomad SAS exome

AF:

0.0463

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.129

AC:

188074

AN:

1461570

Hom.:

13562

Cov.:

AF XY:

0.126

AC XY:

91925

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0932

Gnomad4 AMR exome

AF:

0.0584

Gnomad4 ASJ exome

AF:

0.0454

Gnomad4 EAS exome

AF:

0.0258

Gnomad4 SAS exome

AF:

0.0456

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.120

AC:

18204

AN:

152270

Hom.:

1300

Cov.:

AF XY:

0.124

AC XY:

9235

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0886

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.0324

Gnomad4 SAS

AF:

0.0389

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.0875

Alfa

AF:

0.125

Hom.:

671

Bravo

AF:

0.106

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.138

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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 05, 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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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 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

-0.51

CADD

Benign

5.1

DANN

Benign

0.77

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