chr6-152538508-G-T

Variant names:

• chr6-152538508-G-T
• rs1405695
• NM_182961.4:c.129+1452C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):​c.129+1452C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,660 control chromosomes in the GnomAD database, including 6,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6788 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.898
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 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.129+1452C>A		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.129+1452C>A		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.129+1452C>A		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.129+1452C>A		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000466159.6	TSL:1	c.129+1452C>A		intron	N/A	ENSP00000446021.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43125 AN: 151544 Hom.: 6788 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 43144 AN: 151660 Hom.: 6788 Cov.: 31 AF XY: 0.290 AC XY: 21507 AN XY: 74098

African (AFR) AF: 0.177 AC: 7315 AN: 41330

American (AMR) AF: 0.210 AC: 3207 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2339 AN: 5150

South Asian (SAS) AF: 0.253 AC: 1212 AN: 4794

European-Finnish (FIN) AF: 0.473 AC: 4950 AN: 10468

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22170 AN: 67904

Other (OTH) AF: 0.263 AC: 553 AN: 2104

Alfa AF: 0.312 Hom.: 2078

Bravo AF: 0.261

Asia WGS AF: 0.323 AC: 1123 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.35
PhyloP100		0.90
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: rs1405695; hg19: chr6-152859643;