rs6932325

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.11254-31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,599,144 control chromosomes in the GnomAD database, including 289,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.58 ( 25233 hom., cov: 30)

Exomes 𝑓: 0.60 ( 264380 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.349

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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-152352384-A-C is Benign according to our data. Variant chr6-152352384-A-C is described in ClinVar as [Benign]. Clinvar id is 262153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.11254-31T>G		intron_variant	Intron 69 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 link	c.11254-31T>G	intron_variant	Intron 69 of 145	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 link	c.11209-31T>G	intron_variant	Intron 69 of 145	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1 link	n.4392-31T>G	intron_variant	Intron 12 of 18	1

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87102

AN:

151274

Hom.:

25216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.591

GnomAD3 exomes

AF:

0.583

AC:

142089

AN:

243540

Hom.:

41696

AF XY:

0.582

AC XY:

76647

AN XY:

131778

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.644

Gnomad EAS exome

AF:

0.603

Gnomad SAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.603

AC:

873439

AN:

1447762

Hom.:

264380

Cov.:

AF XY:

0.601

AC XY:

432844

AN XY:

720434

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.601

Gnomad4 ASJ exome

AF:

0.647

Gnomad4 EAS exome

AF:

0.639

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.576

AC:

87161

AN:

151382

Hom.:

25233

Cov.:

AF XY:

0.572

AC XY:

42273

AN XY:

73910

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.613

Gnomad4 ASJ

AF:

0.641

Gnomad4 EAS

AF:

0.619

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.609

Gnomad4 OTH

AF:

0.593

Alfa

AF:

0.538

Hom.:

3386

Bravo

AF:

0.580

Asia WGS

AF:

0.594

AC:

2069

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.90

DANN

Benign

0.29

BranchPoint Hunter

0.0

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