rs9383985

Variant names:

• chr6-152308482-C-T
• rs9383985
• NM_182961.4:c.17346+7G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-152308482-C-T
• chr6-152308482-C-A
• chr6-152308482-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.17346+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,613,560 control chromosomes in the GnomAD database, including 85,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6749 hom., cov: 31)
  • Exomes 𝑓: 0.32 (79224 hom.)
• Consequence: SYNE1 NM_182961.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003899
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.307
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-152308482-C-T is Benign according to our data. Variant chr6-152308482-C-T is described in ClinVar as Benign. ClinVar VariationId is 130412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 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.17346+7G>A		splice_region intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.17133+7G>A		splice_region 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.17346+7G>A		splice_region intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.17133+7G>A		splice_region intron	N/A	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000367256.9	TSL:1	n.1038+7G>A		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41186 AN: 151902 Hom.: 6748 Cov.: 31

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.332 AC: 83373 AN: 251378 AF XY: 0.333

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.585

Gnomad FIN exome AF: 0.360

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.323 AC: 472043 AN: 1461542 Hom.: 79224 Cov.: 53 AF XY: 0.324 AC XY: 235837 AN XY: 727078

African (AFR) AF: 0.0785 AC: 2628 AN: 33476

American (AMR) AF: 0.315 AC: 14101 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 9597 AN: 26130

East Asian (EAS) AF: 0.578 AC: 22947 AN: 39698

South Asian (SAS) AF: 0.329 AC: 28383 AN: 86244

European-Finnish (FIN) AF: 0.354 AC: 18876 AN: 53334

Middle Eastern (MID) AF: 0.299 AC: 1722 AN: 5768

European-Non Finnish (NFE) AF: 0.319 AC: 354165 AN: 1111788

Other (OTH) AF: 0.325 AC: 19624 AN: 60392

GnomAD4 genome AF: 0.271 AC: 41193 AN: 152018 Hom.: 6749 Cov.: 31 AF XY: 0.276 AC XY: 20503 AN XY: 74282

African (AFR) AF: 0.0905 AC: 3754 AN: 41496

American (AMR) AF: 0.293 AC: 4469 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3470

East Asian (EAS) AF: 0.592 AC: 3052 AN: 5156

South Asian (SAS) AF: 0.351 AC: 1688 AN: 4810

European-Finnish (FIN) AF: 0.351 AC: 3698 AN: 10550

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22160 AN: 67952

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.305 Hom.: 18687

Bravo AF: 0.257

Asia WGS AF: 0.429 AC: 1495 AN: 3478

EpiCase AF: 0.316

EpiControl AF: 0.314

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Autosomal recessive ataxia, Beauce type (2)
-	-	2	Emery-Dreifuss muscular dystrophy 4, autosomal dominant (2)
-	-	1	Arthrogryposis multiplex congenita 3, myogenic type (1)
-	-	1	Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.47
DANN	Benign	0.40
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.0

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

Other links and lift over

dbSNP: rs9383985; hg19: chr6-152629617; COSMIC: COSV54931037;