rs214989

Variant names:

• chr6-152417210-A-G
• rs214989
• NM_182961.4:c.5422-195T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):​c.5422-195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,192 control chromosomes in the GnomAD database, including 2,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2575 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet, PanelApp Australia, G2P
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-152417210-A-G is Benign according to our data. Variant chr6-152417210-A-G is described in ClinVar as Benign. ClinVar VariationId is 670642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.5422-195T>C		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.5443-195T>C		intron	N/A	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.5422-195T>C		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.5443-195T>C		intron	N/A	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000461872.6	TSL:1	n.5640-195T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27477 AN: 152074 Hom.: 2575 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27482 AN: 152192 Hom.: 2575 Cov.: 33 AF XY: 0.180 AC XY: 13401 AN XY: 74412

African (AFR) AF: 0.147 AC: 6101 AN: 41528

American (AMR) AF: 0.175 AC: 2676 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5170

South Asian (SAS) AF: 0.275 AC: 1324 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1682 AN: 10584

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13201 AN: 68000

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.194 Hom.: 5898

Bravo AF: 0.178

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.55
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs214989; hg19: chr6-152738345;