Variant 6-152367432-C-T 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 NM_182961.4(SYNE1):c.9808-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,607,646 control chromosomes in the GnomAD database, including 663,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64219 hom., cov: 32)

Exomes 𝑓: 0.91 ( 599668 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.96

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=-0.89).

BP6

Variant 6-152367432-C-T is Benign according to our data. Variant chr6-152367432-C-T is described in ClinVar as [Benign]. Clinvar id is 262206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 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.9808-50G>A		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.9808-50G>A		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.917

AC:

139458

AN:

152158

Hom.:

64154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.964

Gnomad AMI

AF:

0.891

Gnomad AMR

AF:

0.845

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.858

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.936

Gnomad MID

AF:

0.790

Gnomad NFE

AF:

0.923

Gnomad OTH

AF:

0.899

GnomAD3 exomes

AF:

0.869

AC:

214568

AN:

246972

Hom.:

94233

AF XY:

0.867

AC XY:

116127

AN XY:

133920

show subpopulations

Gnomad AFR exome

AF:

0.966

Gnomad AMR exome

AF:

0.746

Gnomad ASJ exome

AF:

0.861

Gnomad EAS exome

AF:

0.856

Gnomad SAS exome

AF:

0.730

Gnomad FIN exome

AF:

0.935

Gnomad NFE exome

AF:

0.922

Gnomad OTH exome

AF:

0.881

GnomAD4 exome

AF:

0.906

AC:

1318425

AN:

1455370

Hom.:

599668

Cov.:

AF XY:

0.901

AC XY:

652889

AN XY:

724390

show subpopulations

Gnomad4 AFR exome

AF:

0.963

Gnomad4 AMR exome

AF:

0.761

Gnomad4 ASJ exome

AF:

0.860

Gnomad4 EAS exome

AF:

0.888

Gnomad4 SAS exome

AF:

0.733

Gnomad4 FIN exome

AF:

0.931

Gnomad4 NFE exome

AF:

0.925

Gnomad4 OTH exome

AF:

0.895

GnomAD4 genome

AF:

0.917

AC:

139585

AN:

152276

Hom.:

64219

Cov.:

AF XY:

0.912

AC XY:

67906

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.964

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.852

Gnomad4 EAS

AF:

0.858

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.936

Gnomad4 NFE

AF:

0.923

Gnomad4 OTH

AF:

0.900

Alfa

AF:

0.915

Hom.:

23126

Bravo

AF:

0.913

Asia WGS

AF:

0.808

AC:

2812

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0010

DANN

Benign

0.55

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