rs9371581

Variant names:

• chr6-152308451-G-A
• rs9371581
• NM_182961.4:c.17346+38C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152308451-G-A
• chr6-152308451-G-C

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+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,612,054 control chromosomes in the GnomAD database, including 220,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18551 hom., cov: 31)
  • Exomes 𝑓: 0.52 (201678 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.48
• Publications: 13 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=-0.78).
• BP6: Variant 6-152308451-G-A is Benign according to our data. Variant chr6-152308451-G-A is described in ClinVar as Benign. ClinVar VariationId is 262172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 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+38C>T		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.17133+38C>T		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+38C>T		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.17133+38C>T		intron	N/A	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000367256.9	TSL:1	n.1038+38C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73241 AN: 151830 Hom.: 18550 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.455

GnomAD2 exomes AF: 0.505 AC: 126889 AN: 251272 AF XY: 0.502

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.501

GnomAD4 exome AF: 0.521 AC: 761057 AN: 1460106 Hom.: 201678 Cov.: 39 AF XY: 0.518 AC XY: 376310 AN XY: 726428

African (AFR) AF: 0.328 AC: 10965 AN: 33468

American (AMR) AF: 0.421 AC: 18839 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 12118 AN: 26118

East Asian (EAS) AF: 0.635 AC: 25199 AN: 39674

South Asian (SAS) AF: 0.384 AC: 33059 AN: 86200

European-Finnish (FIN) AF: 0.679 AC: 36117 AN: 53198

Middle Eastern (MID) AF: 0.396 AC: 2285 AN: 5766

European-Non Finnish (NFE) AF: 0.533 AC: 591961 AN: 1110626

Other (OTH) AF: 0.506 AC: 30514 AN: 60350

GnomAD4 genome AF: 0.482 AC: 73275 AN: 151948 Hom.: 18551 Cov.: 31 AF XY: 0.488 AC XY: 36215 AN XY: 74250

African (AFR) AF: 0.340 AC: 14099 AN: 41454

American (AMR) AF: 0.437 AC: 6669 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3326 AN: 5144

South Asian (SAS) AF: 0.399 AC: 1917 AN: 4810

European-Finnish (FIN) AF: 0.696 AC: 7342 AN: 10556

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36557 AN: 67940

Other (OTH) AF: 0.454 AC: 957 AN: 2110

Alfa AF: 0.511 Hom.: 87877

Bravo AF: 0.459

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.84
PhyloP100		-1.5
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: rs9371581; hg19: chr6-152629586;