rs17082701

Variant names:

• chr6-152450714-G-A
• rs17082701
• NM_182961.4:c.3306C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182961.4(SYNE1):​c.3306C>T​(p.His1102His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,614,018 control chromosomes in the GnomAD database, including 3,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (374 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2802 hom.)
• Consequence: SYNE1 NM_182961.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.484
• Publications: 15 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: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-152450714-G-A is Benign according to our data. Variant chr6-152450714-G-A is described in ClinVar as Benign. ClinVar VariationId is 130439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.484 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 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.3306C>T	p.His1102His	synonymous	Exon 27 of 146	NP_892006.3
	SYNE1	NM_033071.5		c.3327C>T	p.His1109His	synonymous	Exon 27 of 146	NP_149062.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.3306C>T	p.His1102His	synonymous	Exon 27 of 146	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.3327C>T	p.His1109His	synonymous	Exon 27 of 146	ENSP00000396024.1
	SYNE1	ENST00000461872.6	TSL:1	n.3524C>T		non_coding_transcript_exon	Exon 25 of 55

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9808 AN: 152046 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0756

GnomAD2 exomes AF: 0.0562 AC: 14130 AN: 251460 AF XY: 0.0570

Gnomad AFR exome AF: 0.0752

Gnomad AMR exome AF: 0.0354

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.000979

Gnomad FIN exome AF: 0.0568

Gnomad NFE exome AF: 0.0665

Gnomad OTH exome AF: 0.0614

GnomAD4 exome AF: 0.0595 AC: 87031 AN: 1461854 Hom.: 2802 Cov.: 33 AF XY: 0.0594 AC XY: 43181 AN XY: 727230

African (AFR) AF: 0.0762 AC: 2550 AN: 33480

American (AMR) AF: 0.0379 AC: 1694 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2807 AN: 26136

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.0456 AC: 3936 AN: 86258

European-Finnish (FIN) AF: 0.0543 AC: 2903 AN: 53420

Middle Eastern (MID) AF: 0.0640 AC: 369 AN: 5762

European-Non Finnish (NFE) AF: 0.0621 AC: 69045 AN: 1111978

Other (OTH) AF: 0.0615 AC: 3714 AN: 60396

GnomAD4 genome AF: 0.0646 AC: 9824 AN: 152164 Hom.: 374 Cov.: 32 AF XY: 0.0630 AC XY: 4685 AN XY: 74372

African (AFR) AF: 0.0722 AC: 2998 AN: 41522

American (AMR) AF: 0.0583 AC: 891 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5162

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4820

European-Finnish (FIN) AF: 0.0532 AC: 563 AN: 10584

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4608 AN: 68004

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

Alfa AF: 0.0672 Hom.: 621

Bravo AF: 0.0644

Asia WGS AF: 0.0350 AC: 121 AN: 3478

EpiCase AF: 0.0678

EpiControl AF: 0.0679

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	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)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.37
PhyloP100		-0.48
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: rs17082701; hg19: chr6-152771849; COSMIC: COSV55005635; COSMIC: COSV55005635;