rs117020413

Variant names:

• chr6-152376540-G-T
• rs117020413
• NM_182961.4:c.9165C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-152376540-G-T
• chr6-152376540-G-A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BS1 BS2

The NM_182961.4(SYNE1):​c.9165C>A​(p.Ser3055Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,613,918 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (13 hom., cov: 32)
  • Exomes 𝑓: 0.013 (180 hom.)
• Consequence: SYNE1 NM_182961.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.29
• Publications: 5 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.256).
• BP6: Variant 6-152376540-G-T is Benign according to our data. Variant chr6-152376540-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00867 (1320/152204) while in subpopulation SAS AF = 0.0266 (128/4816). AF 95% confidence interval is 0.0228. There are 13 homozygotes in GnomAd4. There are 655 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR,AD gene

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.9165C>A	p.Ser3055Ser	synonymous	Exon 58 of 146	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.9186C>A	p.Ser3062Ser	synonymous	Exon 58 of 146	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.9165C>A	p.Ser3055Ser	synonymous	Exon 58 of 146	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.9186C>A	p.Ser3062Ser	synonymous	Exon 58 of 146	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000454018.7	TSL:1	c.516C>A	p.Ser172Ser	synonymous	Exon 4 of 8	ENSP00000390858.4	A0A0C4DH48

Frequencies

GnomAD3 genomes AF: 0.00867 AC: 1319 AN: 152086 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.0122 AC: 3075 AN: 251136 AF XY: 0.0138

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.0110

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.00997

GnomAD4 exome AF: 0.0133 AC: 19489 AN: 1461714 Hom.: 180 Cov.: 30 AF XY: 0.0138 AC XY: 10064 AN XY: 727166

African (AFR) AF: 0.00218 AC: 73 AN: 33480

American (AMR) AF: 0.00425 AC: 190 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00964 AC: 252 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0318 AC: 2739 AN: 86252

European-Finnish (FIN) AF: 0.0134 AC: 713 AN: 53286

Middle Eastern (MID) AF: 0.0177 AC: 102 AN: 5768

European-Non Finnish (NFE) AF: 0.0132 AC: 14669 AN: 1111982

Other (OTH) AF: 0.0124 AC: 750 AN: 60396

GnomAD4 genome AF: 0.00867 AC: 1320 AN: 152204 Hom.: 13 Cov.: 32 AF XY: 0.00880 AC XY: 655 AN XY: 74400

African (AFR) AF: 0.00221 AC: 92 AN: 41548

American (AMR) AF: 0.00451 AC: 69 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0266 AC: 128 AN: 4816

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10572

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 859 AN: 68018

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00994 Hom.: 9

Bravo AF: 0.00736

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0128

EpiControl AF: 0.0138

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Autosomal recessive ataxia, Beauce type (1)
-	-	1	Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)
-	-	1	Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		1.3
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs117020413; hg19: chr6-152697675; COSMIC: COSV108092183;