rs147380321

Variant names:

• chr6-152139913-CTGTT-C
• rs147380321
• NM_182961.4:c.25458+33_25458+36delAACA

Your query was ambiguous. Multiple possible variants found:

• chr6-152139913-CTGTT-C
• chr6-152139913-CTGTT-CTGTTTGTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.25458+33_25458+36delAACA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,609,670 control chromosomes in the GnomAD database, including 128,539 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14403 hom., cov: 0)
  • Exomes 𝑓: 0.39 (114136 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• Publications: 1 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

ENSG00000300811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 6-152139913-CTGTT-C is Benign according to our data. Variant chr6-152139913-CTGTT-C is described in ClinVar as Benign. ClinVar VariationId is 262194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 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.25458+33_25458+36delAACA		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_001347702.2	MANE Plus Clinical	c.1992+33_1992+36delAACA		intron	N/A	NP_001334631.1	F8WAI0
	SYNE1	NM_033071.5		c.25314+33_25314+36delAACA		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.25458+33_25458+36delAACA		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000354674.5	TSL:5 MANE Plus Clinical	c.1992+33_1992+36delAACA		intron	N/A	ENSP00000346701.4	F8WAI0
	SYNE1	ENST00000423061.6	TSL:1	c.25314+33_25314+36delAACA		intron	N/A	ENSP00000396024.1	A0A0C4DG40

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64832 AN: 151286 Hom.: 14402 Cov.: 0

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.407 AC: 101053 AN: 248474 AF XY: 0.403

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.531

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.392 AC: 571247 AN: 1458264 Hom.: 114136 AF XY: 0.393 AC XY: 285313 AN XY: 725494

African (AFR) AF: 0.524 AC: 17496 AN: 33378

American (AMR) AF: 0.532 AC: 23725 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 13297 AN: 26124

East Asian (EAS) AF: 0.308 AC: 12240 AN: 39682

South Asian (SAS) AF: 0.450 AC: 38724 AN: 86080

European-Finnish (FIN) AF: 0.249 AC: 13278 AN: 53320

Middle Eastern (MID) AF: 0.488 AC: 2122 AN: 4346

European-Non Finnish (NFE) AF: 0.384 AC: 425892 AN: 1110540

Other (OTH) AF: 0.407 AC: 24473 AN: 60172

GnomAD4 genome AF: 0.429 AC: 64883 AN: 151406 Hom.: 14403 Cov.: 0 AF XY: 0.425 AC XY: 31434 AN XY: 73994

African (AFR) AF: 0.525 AC: 21642 AN: 41246

American (AMR) AF: 0.498 AC: 7575 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1575 AN: 5108

South Asian (SAS) AF: 0.436 AC: 2085 AN: 4782

European-Finnish (FIN) AF: 0.245 AC: 2582 AN: 10550

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26236 AN: 67744

Other (OTH) AF: 0.467 AC: 979 AN: 2098

Alfa AF: 0.415 Hom.: 2389

Bravo AF: 0.458

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
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: rs147380321; hg19: chr6-152461048;