6-152318049-C-G

Variant names:

• chr6-152318049-C-G
• rs17082448
• NM_182961.4:c.16572+32G>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.16572+32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 1,613,796 control chromosomes in the GnomAD database, including 3,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (887 hom., cov: 32)
  • Exomes 𝑓: 0.047 (2258 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.274
• 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: 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 6-152318049-C-G is Benign according to our data. Variant chr6-152318049-C-G is described in ClinVar as Benign. ClinVar VariationId is 262169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.16572+32G>C		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.16359+32G>C		intron	N/A	NP_149062.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.16572+32G>C		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.16359+32G>C		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000367256.9	TSL:1	n.264+32G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12434 AN: 152094 Hom.: 881 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0640

GnomAD2 exomes AF: 0.0462 AC: 11566 AN: 250350 AF XY: 0.0446

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.0214

Gnomad ASJ exome AF: 0.0420

Gnomad EAS exome AF: 0.0284

Gnomad FIN exome AF: 0.0154

Gnomad NFE exome AF: 0.0410

Gnomad OTH exome AF: 0.0374

GnomAD4 exome AF: 0.0473 AC: 69061 AN: 1461584 Hom.: 2258 Cov.: 31 AF XY: 0.0463 AC XY: 33666 AN XY: 727128

African (AFR) AF: 0.210 AC: 7040 AN: 33478

American (AMR) AF: 0.0239 AC: 1069 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 1068 AN: 26132

East Asian (EAS) AF: 0.0323 AC: 1281 AN: 39692

South Asian (SAS) AF: 0.0454 AC: 3920 AN: 86252

European-Finnish (FIN) AF: 0.0157 AC: 838 AN: 53418

Middle Eastern (MID) AF: 0.0406 AC: 233 AN: 5736

European-Non Finnish (NFE) AF: 0.0453 AC: 50401 AN: 1111780

Other (OTH) AF: 0.0532 AC: 3211 AN: 60372

GnomAD4 genome AF: 0.0819 AC: 12467 AN: 152212 Hom.: 887 Cov.: 32 AF XY: 0.0795 AC XY: 5915 AN XY: 74434

African (AFR) AF: 0.197 AC: 8185 AN: 41498

American (AMR) AF: 0.0334 AC: 511 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.0265 AC: 137 AN: 5178

South Asian (SAS) AF: 0.0514 AC: 248 AN: 4822

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0425 AC: 2894 AN: 68026

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0585 Hom.: 81

Bravo AF: 0.0877

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.47
PhyloP100		-0.27
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: rs17082448; hg19: chr6-152639184;