6-152152046-T-C

Position:

chr6-152152046-T-C

Variant summary

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

The NM_182961.4(SYNE1):c.24225A>G(p.Ala8075Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,614,170 control chromosomes in the GnomAD database, including 1,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 193 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1415 hom. )

Consequence

SYNE1
NM_182961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.02

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=-0.9).

BP6

Variant 6-152152046-T-C is Benign according to our data. Variant chr6-152152046-T-C is described in ClinVar as [Benign]. Clinvar id is 130425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152152046-T-C is described in Lovd as [Benign]. Variant chr6-152152046-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 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.24225A>G	p.Ala8075Ala	synonymous_variant	134/146	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2 linkuse as main transcript	c.690A>G	p.Ala230Ala	synonymous_variant	5/18	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.24225A>G	p.Ala8075Ala	synonymous_variant	134/146	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1
SYNE1	ENST00000354674.5 linkuse as main transcript	c.690A>G	p.Ala230Ala	synonymous_variant	5/18	5	NM_001347702.2	ENSP00000346701.4		F8WAI0

Frequencies

GnomAD3 genomes

AF:

0.0472

AC:

7185

AN:

152168

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0519

Gnomad ASJ

AF:

0.0928

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.0427

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0414

Gnomad OTH

AF:

0.0593

GnomAD3 exomes

AF:

0.0397

AC:

9975

AN:

251452

Hom.:

257

AF XY:

0.0390

AC XY:

5299

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0623

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0881

Gnomad EAS exome

AF:

0.000816

Gnomad SAS exome

AF:

0.0195

Gnomad FIN exome

AF:

0.0431

Gnomad NFE exome

AF:

0.0444

Gnomad OTH exome

AF:

0.0487

GnomAD4 exome

AF:

0.0410

AC:

59956

AN:

1461884

Hom.:

1415

Cov.:

AF XY:

0.0404

AC XY:

29392

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0621

Gnomad4 AMR exome

AF:

0.0356

Gnomad4 ASJ exome

AF:

0.0933

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0191

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0420

Gnomad4 OTH exome

AF:

0.0470

GnomAD4 genome

AF:

0.0473

AC:

7206

AN:

152286

Hom.:

193

Cov.:

AF XY:

0.0470

AC XY:

3501

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0613

Gnomad4 AMR

AF:

0.0517

Gnomad4 ASJ

AF:

0.0928

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0188

Gnomad4 FIN

AF:

0.0427

Gnomad4 NFE

AF:

0.0414

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0458

Hom.:

221

Bravo

AF:

0.0482

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.0454

EpiControl

AF:

0.0501

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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	Feb 04, 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	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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 31, 2024

- -

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

-0.90

CADD

Benign

0.039

DANN

Benign

0.26

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