6-152362278-G-T

Position:

chr6-152362278-G-T

Variant summary

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

The NM_182961.4(SYNE1):c.10191C>A(p.Gly3397Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,613,830 control chromosomes in the GnomAD database, including 367,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32077 hom., cov: 32)

Exomes 𝑓: 0.68 ( 335469 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.240

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 6-152362278-G-T is Benign according to our data. Variant chr6-152362278-G-T is described in ClinVar as [Benign]. Clinvar id is 130388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152362278-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4 linkuse as main transcript	c.10191C>A	p.Gly3397Gly	synonymous_variant	64/146	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.10191C>A	p.Gly3397Gly	synonymous_variant	64/146	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.10212C>A	p.Gly3404Gly	synonymous_variant	64/146	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1 linkuse as main transcript	n.3329C>A		non_coding_transcript_exon_variant	7/19	1

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98434

AN:

151898

Hom.:

32056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.674

GnomAD3 exomes

AF:

0.659

AC:

165821

AN:

251456

Hom.:

55170

AF XY:

0.658

AC XY:

89418

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.577

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.789

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.670

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.676

AC:

988107

AN:

1461814

Hom.:

335469

Cov.:

AF XY:

0.674

AC XY:

489812

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.574

Gnomad4 AMR exome

AF:

0.671

Gnomad4 ASJ exome

AF:

0.710

Gnomad4 EAS exome

AF:

0.822

Gnomad4 SAS exome

AF:

0.596

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.674

GnomAD4 genome

AF:

0.648

AC:

98507

AN:

152016

Hom.:

32077

Cov.:

AF XY:

0.643

AC XY:

47803

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.676

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.793

Gnomad4 SAS

AF:

0.609

Gnomad4 FIN

AF:

0.591

Gnomad4 NFE

AF:

0.677

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.665

Hom.:

61556

Bravo

AF:

0.652

Asia WGS

AF:

0.700

AC:

2437

AN:

3478

EpiCase

AF:

0.669

EpiControl

AF:

0.662

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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. -

Autosomal recessive ataxia, Beauce type

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

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

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 02, 2018

- -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.021

DANN

Benign

0.29

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