rs13211987

Variant names:

• chr6-152134963-G-A
• rs13211987
• NM_182961.4:c.25788+141C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152134963-G-A
• chr6-152134963-G-T

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.25788+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,089,152 control chromosomes in the GnomAD database, including 10,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1039 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8995 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.199
• Publications: 3 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

ENSG00000300811 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-152134963-G-A is Benign according to our data. Variant chr6-152134963-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.25788+141C>T		intron	N/A	NP_892006.3
	SYNE1	NM_001347702.2	MANE Plus Clinical	c.2322+141C>T		intron	N/A	NP_001334631.1
	SYNE1	NM_033071.5		c.25644+141C>T		intron	N/A	NP_149062.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.25788+141C>T		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000354674.5	TSL:5 MANE Plus Clinical	c.2322+141C>T		intron	N/A	ENSP00000346701.4
	SYNE1	ENST00000423061.6	TSL:1	c.25644+141C>T		intron	N/A	ENSP00000396024.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15842 AN: 151824 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0825

GnomAD4 exome AF: 0.133 AC: 124456 AN: 937208 Hom.: 8995 Cov.: 12 AF XY: 0.131 AC XY: 62981 AN XY: 480850

African (AFR) AF: 0.0371 AC: 787 AN: 21234

American (AMR) AF: 0.0443 AC: 1383 AN: 31226

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2224 AN: 20762

East Asian (EAS) AF: 0.0880 AC: 3054 AN: 34688

South Asian (SAS) AF: 0.0860 AC: 5551 AN: 64580

European-Finnish (FIN) AF: 0.195 AC: 8344 AN: 42732

Middle Eastern (MID) AF: 0.0574 AC: 255 AN: 4440

European-Non Finnish (NFE) AF: 0.145 AC: 97904 AN: 674940

Other (OTH) AF: 0.116 AC: 4954 AN: 42606

GnomAD4 genome AF: 0.104 AC: 15853 AN: 151944 Hom.: 1039 Cov.: 32 AF XY: 0.103 AC XY: 7648 AN XY: 74264

African (AFR) AF: 0.0416 AC: 1724 AN: 41460

American (AMR) AF: 0.0579 AC: 884 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.0602 AC: 310 AN: 5152

South Asian (SAS) AF: 0.0876 AC: 420 AN: 4794

European-Finnish (FIN) AF: 0.194 AC: 2046 AN: 10550

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9770 AN: 67950

Other (OTH) AF: 0.0849 AC: 179 AN: 2108

Alfa AF: 0.118 Hom.: 195

Bravo AF: 0.0896

Asia WGS AF: 0.0890 AC: 313 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.86
DANN	Benign	0.20
PhyloP100		-0.20
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: rs13211987; hg19: chr6-152456098; COSMIC: COSV55015752;