rs214943

Positions:

• chr6-152390260-T-A
• chr6-152390260-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.8177+20A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,612,516 control chromosomes in the GnomAD database, including 140,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (19389 hom., cov: 31)
  • Exomes 𝑓: 0.40 (121055 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.781

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-152390260-T-A is Benign according to our data. Variant chr6-152390260-T-A is described in ClinVar as [Benign]. Clinvar id is 262201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152390260-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.8177+20A>T		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.8177+20A>T		intron_variant		1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.8198+20A>T		intron_variant		1		ENSP00000396024.1
SYNE1	ENST00000461872.6	n.8395+20A>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72910 AN: 151760 Hom.: 19366 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.466

GnomAD3 exomes AF: 0.432 AC: 108251 AN: 250648 Hom.: 25737 AF XY: 0.432 AC XY: 58592 AN XY: 135506

Gnomad AFR exome AF: 0.697

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.769

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.391

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.396 AC: 579075 AN: 1460640 Hom.: 121055 Cov.: 35 AF XY: 0.399 AC XY: 289914 AN XY: 726652

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.481 AC: 72984 AN: 151876 Hom.: 19389 Cov.: 31 AF XY: 0.482 AC XY: 35738 AN XY: 74216

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.466

Alfa AF: 0.319 Hom.: 1276

Bravo AF: 0.488

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	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. -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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	-0.86
CADD	Benign	4.1
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs214943; hg19: chr6-152711395; COSMIC: COSV54945465;