Variant 6-152206120-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.23019+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,571,386 control chromosomes in the GnomAD database, including 1,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 582 hom., cov: 33)

Exomes 𝑓: 0.012 ( 864 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.189

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=-0.87).

BP6

Variant 6-152206120-C-T is Benign according to our data. Variant chr6-152206120-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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.23019+48G>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.23019+48G>A		intron_variant		1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7942

AN:

152180

Hom.:

580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0515

Gnomad SAS

AF:

0.0801

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0269

AC:

6364

AN:

236986

Hom.:

325

AF XY:

0.0267

AC XY:

3422

AN XY:

128196

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.00888

Gnomad ASJ exome

AF:

0.00214

Gnomad EAS exome

AF:

0.0460

Gnomad SAS exome

AF:

0.0712

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

AF:

0.0123

AC:

17396

AN:

1419088

Hom.:

864

Cov.:

AF XY:

0.0135

AC XY:

9552

AN XY:

707482

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.00194

Gnomad4 EAS exome

AF:

0.0727

Gnomad4 SAS exome

AF:

0.0663

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.000923

Gnomad4 OTH exome

AF:

0.0208

GnomAD4 genome

AF:

0.0523

AC:

7967

AN:

152298

Hom.:

582

Cov.:

AF XY:

0.0540

AC XY:

4019

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0518

Gnomad4 SAS

AF:

0.0796

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0558

Asia WGS

AF:

0.0650

AC:

225

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.29

DANN

Benign

0.71

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