NM_182961.4:c.9147-13G>A

Variant names:

• chr6-152376571-C-T
• rs214955
• NM_182961.4:c.9147-13G>A

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.9147-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,611,968 control chromosomes in the GnomAD database, including 182,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19085 hom., cov: 32)
  • Exomes 𝑓: 0.47 (163729 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.559
• Publications: 31 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=-0.87).
• BP6: Variant 6-152376571-C-T is Benign according to our data. Variant chr6-152376571-C-T is described in ClinVar as Benign. ClinVar VariationId is 262202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 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.9147-13G>A		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.9168-13G>A		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.9147-13G>A		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.9168-13G>A		intron	N/A	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000454018.7	TSL:1	c.498-13G>A		intron	N/A	ENSP00000390858.4	A0A0C4DH48

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75863 AN: 151736 Hom.: 19064 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.508

GnomAD2 exomes AF: 0.504 AC: 125908 AN: 249794 AF XY: 0.506

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.513

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.471 AC: 687474 AN: 1460114 Hom.: 163729 Cov.: 41 AF XY: 0.475 AC XY: 344916 AN XY: 726414

African (AFR) AF: 0.561 AC: 18755 AN: 33450

American (AMR) AF: 0.503 AC: 22458 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 11996 AN: 26130

East Asian (EAS) AF: 0.541 AC: 21454 AN: 39670

South Asian (SAS) AF: 0.595 AC: 51279 AN: 86200

European-Finnish (FIN) AF: 0.513 AC: 27035 AN: 52694

Middle Eastern (MID) AF: 0.595 AC: 3428 AN: 5766

European-Non Finnish (NFE) AF: 0.452 AC: 501831 AN: 1111170

Other (OTH) AF: 0.484 AC: 29238 AN: 60358

GnomAD4 genome AF: 0.500 AC: 75928 AN: 151854 Hom.: 19085 Cov.: 32 AF XY: 0.504 AC XY: 37380 AN XY: 74186

African (AFR) AF: 0.548 AC: 22670 AN: 41388

American (AMR) AF: 0.479 AC: 7309 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1629 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2796 AN: 5160

South Asian (SAS) AF: 0.582 AC: 2796 AN: 4808

European-Finnish (FIN) AF: 0.524 AC: 5511 AN: 10518

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31551 AN: 67946

Other (OTH) AF: 0.508 AC: 1069 AN: 2106

Alfa AF: 0.474 Hom.: 73680

Bravo AF: 0.498

Asia WGS AF: 0.526 AC: 1828 AN: 3478

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	15
DANN	Benign	0.48
PhyloP100		0.56
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: rs214955; hg19: chr6-152697706; COSMIC: COSV54939413; COSMIC: COSV54939413;