rs144596829

Variant names:

• chr6-152347080-C-T
• rs144596829
• NM_182961.4:c.12057G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-152347080-C-T
• chr6-152347080-C-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_182961.4(SYNE1):​c.12057G>A​(p.Ala4019Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,614,170 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (120 hom.)
• Consequence: SYNE1 NM_182961.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.71
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-152347080-C-T is Benign according to our data. Variant chr6-152347080-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 130395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 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.12057G>A	p.Ala4019Ala	synonymous	Exon 73 of 146	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.11844G>A	p.Ala3948Ala	synonymous	Exon 72 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.12057G>A	p.Ala4019Ala	synonymous	Exon 73 of 146	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.11844G>A	p.Ala3948Ala	synonymous	Exon 72 of 146	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000471834.1	TSL:1	n.5195G>A		non_coding_transcript_exon	Exon 16 of 19

Frequencies

GnomAD3 genomes AF: 0.00886 AC: 1348 AN: 152184 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00890 AC: 2237 AN: 251466 AF XY: 0.00908

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00665

Gnomad ASJ exome AF: 0.00685

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.0112 AC: 16437 AN: 1461868 Hom.: 120 Cov.: 31 AF XY: 0.0110 AC XY: 8023 AN XY: 727234

African (AFR) AF: 0.00227 AC: 76 AN: 33478

American (AMR) AF: 0.00644 AC: 288 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00597 AC: 156 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00303 AC: 261 AN: 86254

European-Finnish (FIN) AF: 0.00996 AC: 532 AN: 53420

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5758

European-Non Finnish (NFE) AF: 0.0130 AC: 14442 AN: 1112004

Other (OTH) AF: 0.0101 AC: 610 AN: 60394

GnomAD4 genome AF: 0.00885 AC: 1348 AN: 152302 Hom.: 6 Cov.: 32 AF XY: 0.00818 AC XY: 609 AN XY: 74478

African (AFR) AF: 0.00243 AC: 101 AN: 41564

American (AMR) AF: 0.00863 AC: 132 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.00989 AC: 105 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 951 AN: 68032

Other (OTH) AF: 0.0133 AC: 28 AN: 2106

Alfa AF: 0.00982 Hom.: 5

Bravo AF: 0.00864

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0123

EpiControl AF: 0.0113

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	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	-0.59
CADD	Benign	0.18
DANN	Benign	0.75
PhyloP100		-1.7
Mutation Taster		=88/12	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs144596829; hg19: chr6-152668215;