Variant rs4331993 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000367255.10(SYNE1):c.1351-24A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,557,906 control chromosomes in the GnomAD database, including 65,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11878 hom., cov: 30)

Exomes 𝑓: 0.33 ( 53665 hom. )

Consequence

SYNE1
ENST00000367255.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.63

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

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-152472437-T-A is Benign according to our data. Variant chr6-152472437-T-A is described in ClinVar as [Benign]. Clinvar id is 262162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 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.1351-24A>T		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.1351-24A>T		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

58761

AN:

150828

Hom.:

11871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.751

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.338

AC:

80749

AN:

238760

Hom.:

8958

AF XY:

0.340

AC XY:

43819

AN XY:

128720

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.612

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.330

AC:

464463

AN:

1406962

Hom.:

53665

Cov.:

AF XY:

0.333

AC XY:

233500

AN XY:

701478

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.632

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.390

AC:

58807

AN:

150944

Hom.:

11878

Cov.:

AF XY:

0.392

AC XY:

28843

AN XY:

73670

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.751

Gnomad4 SAS

AF:

0.494

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.123

Hom.:

403

Bravo

AF:

0.394

Asia WGS

AF:

0.557

AC:

1940

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

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

-0.77

CADD

Benign

0.012

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