rs34905593

Positions:

chr6-152233922-T-A

Variant summary

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

The NM_182961.4(SYNE1):c.20571A>T(p.Ser6857Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,614,078 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 35 hom., cov: 32)

Exomes 𝑓: 0.022 ( 426 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.658

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:

SYNE1 (HGNC:):

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=-0.54).

BP6

Variant 6-152233922-T-A is Benign according to our data. Variant chr6-152233922-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 130418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152233922-T-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.658 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0171 (2598/152274) while in subpopulation NFE AF= 0.025 (1702/68012). AF 95% confidence interval is 0.024. There are 35 homozygotes in gnomad4. There are 1314 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2598 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.20571A>T	p.Ser6857Ser	synonymous_variant	112/146	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.20571A>T	p.Ser6857Ser	synonymous_variant	112/146	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.20358A>T	p.Ser6786Ser	synonymous_variant	111/146	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000367256.9 linkuse as main transcript	n.4263A>T		non_coding_transcript_exon_variant	27/61	1
SYNE1	ENST00000409694.6 linkuse as main transcript	n.4155A>T		non_coding_transcript_exon_variant	25/59	1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2599

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.0196

AC:

4935

AN:

251310

Hom.:

AF XY:

0.0211

AC XY:

2863

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.00864

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0242

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0248

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0223

AC:

32628

AN:

1461804

Hom.:

426

Cov.:

AF XY:

0.0225

AC XY:

16375

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00367

Gnomad4 AMR exome

AF:

0.00843

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0236

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0171

AC:

2598

AN:

152274

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1314

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0238

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.0250

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 01, 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	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 23, 2013	- -

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 26, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive ataxia, Beauce type

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. -

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

Aug 11, 2021

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.12

DANN

Benign

0.66

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