rs6934016

Variant names:

• chr6-152135893-C-A
• rs6934016
• NM_182961.4:c.25660-661G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152135893-C-A
• chr6-152135893-C-T

Variant summary

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

The NM_182961.4(SYNE1):​c.25660-661G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,128 control chromosomes in the GnomAD database, including 1,206 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 0.12 (1206 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 4 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

ENSG00000300811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.25660-661G>T		intron_variant	Intron 141 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.2194-661G>T		intron_variant	Intron 13 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.25660-661G>T		intron_variant	Intron 141 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.2194-661G>T		intron_variant	Intron 13 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18256 AN: 152010 Hom.: 1197 Cov.: 32

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.120 AC: 18308 AN: 152128 Hom.: 1206 Cov.: 32 AF XY: 0.119 AC XY: 8863 AN XY: 74356

African (AFR) AF: 0.0980 AC: 4065 AN: 41494

American (AMR) AF: 0.0643 AC: 984 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3472

East Asian (EAS) AF: 0.0590 AC: 305 AN: 5172

South Asian (SAS) AF: 0.0871 AC: 419 AN: 4810

European-Finnish (FIN) AF: 0.192 AC: 2033 AN: 10572

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9776 AN: 67988

Other (OTH) AF: 0.0971 AC: 205 AN: 2112

Alfa AF: 0.131 Hom.: 5475

Bravo AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.38
PhyloP100		-0.21
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: rs6934016; hg19: chr6-152457028;