6-152201238-G-C

Variant names:

• chr6-152201238-G-C
• rs719764
• NM_182961.4:c.23145+586C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):​c.23145+586C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,902 control chromosomes in the GnomAD database, including 25,803 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25803 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 2 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: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.654 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.23145+586C>G		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.22932+586C>G		intron	N/A	NP_149062.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.23145+586C>G		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.22932+586C>G		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000367251.7	TSL:1	c.1911+586C>G		intron	N/A	ENSP00000356220.3

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88064 AN: 151784 Hom.: 25767 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.580 AC: 88164 AN: 151902 Hom.: 25803 Cov.: 31 AF XY: 0.576 AC XY: 42763 AN XY: 74216

African (AFR) AF: 0.575 AC: 23807 AN: 41414

American (AMR) AF: 0.665 AC: 10153 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2029 AN: 3472

East Asian (EAS) AF: 0.645 AC: 3320 AN: 5148

South Asian (SAS) AF: 0.590 AC: 2835 AN: 4804

European-Finnish (FIN) AF: 0.450 AC: 4742 AN: 10534

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39277 AN: 67948

Other (OTH) AF: 0.613 AC: 1293 AN: 2110

Alfa AF: 0.450 Hom.: 1144

Bravo AF: 0.603

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.013
DANN	Benign	0.40
PhyloP100		-2.6
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: rs719764; hg19: chr6-152522373;