Variant chr6-152236976-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.20068-29_20068-28insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,611,122 control chromosomes in the GnomAD database, including 39,899 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3550 hom., cov: 28)

Exomes 𝑓: 0.22 ( 36349 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.407

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 -16 ACMG points.

BP6

Variant 6-152236976-T-TA is Benign according to our data. Variant chr6-152236976-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 262177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.353 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.20068-29_20068-28insT		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 linkuse as main transcript	c.20068-29_20068-28insT	intron_variant	1	NM_182961.4	ENSP00000356224	P1	Q8NF91-1
SYNE1	ENST00000423061.6 linkuse as main transcript	c.19855-29_19855-28insT	intron_variant	1		ENSP00000396024
SYNE1	ENST00000367256.9 linkuse as main transcript	n.3760-29_3760-28insT	intron_variant, non_coding_transcript_variant	1
SYNE1	ENST00000409694.6 linkuse as main transcript	n.3652-29_3652-28insT	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29807

AN:

151958

Hom.:

3542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.243

AC:

59990

AN:

246790

Hom.:

8327

AF XY:

0.237

AC XY:

31530

AN XY:

133316

show subpopulations

Gnomad AFR exome

AF:

0.0769

Gnomad AMR exome

AF:

0.451

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.220

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.217

AC:

317291

AN:

1459046

Hom.:

36349

Cov.:

AF XY:

0.217

AC XY:

157444

AN XY:

725758

show subpopulations

Gnomad4 AFR exome

AF:

0.0764

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.196

AC:

29839

AN:

152076

Hom.:

3550

Cov.:

AF XY:

0.202

AC XY:

15030

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0792

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.151

Hom.:

437

Asia WGS

AF:

0.243

AC:

846

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely 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

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