chr6-152256617-T-C

Variant names:

• chr6-152256617-T-C
• rs17082389
• NM_182961.4:c.19104+17A>G

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.19104+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,612,740 control chromosomes in the GnomAD database, including 3,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (319 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3597 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.41
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-152256617-T-C is Benign according to our data. Variant chr6-152256617-T-C is described in ClinVar as Benign. ClinVar VariationId is 262175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 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.19104+17A>G		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.18891+17A>G		intron	N/A	NP_149062.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.19104+17A>G		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.18891+17A>G		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000367256.9	TSL:1	n.2796+17A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9214 AN: 152080 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0717

GnomAD2 exomes AF: 0.0680 AC: 17087 AN: 251346 AF XY: 0.0723

Gnomad AFR exome AF: 0.0610

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.0218

Gnomad NFE exome AF: 0.0595

Gnomad OTH exome AF: 0.0761

GnomAD4 exome AF: 0.0647 AC: 94476 AN: 1460542 Hom.: 3597 Cov.: 31 AF XY: 0.0671 AC XY: 48777 AN XY: 726554

African (AFR) AF: 0.0591 AC: 1976 AN: 33452

American (AMR) AF: 0.0356 AC: 1592 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2952 AN: 26078

East Asian (EAS) AF: 0.137 AC: 5442 AN: 39638

South Asian (SAS) AF: 0.128 AC: 11042 AN: 86204

European-Finnish (FIN) AF: 0.0226 AC: 1202 AN: 53204

Middle Eastern (MID) AF: 0.122 AC: 703 AN: 5758

European-Non Finnish (NFE) AF: 0.0585 AC: 64977 AN: 1111196

Other (OTH) AF: 0.0761 AC: 4590 AN: 60322

GnomAD4 genome AF: 0.0606 AC: 9220 AN: 152198 Hom.: 319 Cov.: 32 AF XY: 0.0607 AC XY: 4520 AN XY: 74428

African (AFR) AF: 0.0616 AC: 2556 AN: 41518

American (AMR) AF: 0.0466 AC: 713 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.126 AC: 653 AN: 5172

South Asian (SAS) AF: 0.115 AC: 556 AN: 4814

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10620

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3893 AN: 67996

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0632 Hom.: 366

Bravo AF: 0.0634

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Autosomal recessive ataxia, Beauce type;C2751807: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	-0.91
CADD	Benign	0.086
DANN	Benign	0.34
PhyloP100		-1.4
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: rs17082389; hg19: chr6-152577752; COSMIC: COSV54935033;