rs75817012

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_182961.4(SYNE1):c.2697A>G(p.Arg899=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,614,122 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00079 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00098 ( 36 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.549

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 (MetaRNN=0.0037485063).

BP6

Variant 6-152455916-T-C is Benign according to our data. Variant chr6-152455916-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 284389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152455916-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.549 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000794 (121/152312) while in subpopulation EAS AF= 0.0224 (116/5176). AF 95% confidence interval is 0.0191. There are 1 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.2697A>G	p.Arg899=	synonymous_variant	23/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.2697A>G	p.Arg899=	synonymous_variant	23/146	1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0224

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00179

AC:

449

AN:

251394

Hom.:

AF XY:

0.00163

AC XY:

222

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0241

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000978

AC:

1430

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

693

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0345

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000794

AC:

121

AN:

152312

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000895

ExAC

AF:

0.00185

AC:

225

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 23, 2015

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 28, 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. -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant;C5193121:Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 07, 2022

- -

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_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

Cadd

Benign

6.2

Dann

Benign

0.86

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;N

REVEL

Benign

0.030

Sift4G

Benign

0.58

Vest4

0.075

MVP

0.41

ClinPred

0.024

GERP RS

-1.3

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